Schizophrenia, Schizoaffective Disorder
Conditions
Brief summary
This study investigates the effects of RO6889450 on the negative symptoms associated with schizophrenia and schizoaffective disorder.
Interventions
DRUGRO6889450
Participants will receive a once-daily, oral dose of RO6889450 for 12 weeks.
DRUGPlacebo
Participants will receive a once-daily, oral dose of placebo matched to RO6889450 for 12 weeks.
Sponsors
Hoffmann-La Roche
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 55 Years
Healthy volunteers
No
Inclusion criteria
* Patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis of schizophrenia or schizoaffective disorder as confirmed by the Mini International Neuropsychiatric Interview (MINI) * Part B only: Stable treatment with a dopamine/serotonin (D2/5HT2A) antagonist or pure D2 antagonist(s), or a D2 partial agonist for a minimum of 6 months and receiving no more than two antipsychotics * Medically stable during the 3 months prior to study entry * Participant is an outpatient with no psychiatric hospitalizations within the prior 6 months * PANSS negative symptom factor score of 18 or higher * The following rating on items of the PANSS: (a) less than 5 on G8 (uncooperativeness), P1 (delusions), P3 (hallucinations), P4 (excitement/hyperactivity), and P6 (suspiciousness/persecution); (b) less than 4 on P7 (hostility), and G14 (poor impulse control) * Has an informant who is considered reliable by the Investigator * Body mass index (BMI) between 18-40 kg/m2 inclusive * Female participants are eligible to participate if not pregnant, not breastfeeding and 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
Exclusion criteria
* Moderate to severe substance use disorder within six months of study entry (excluding nicotine or caffeine) as defined by DSM-5 * Extrapyramidal symptom rating scale (ESRS-A CGI) subscore greater than or equal to 3 * Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder) * PANSS item G6 (depression) greater than or equal to 5 * Significant risk of suicide or harming him- or herself or others according to the Investigator's judgment * A prior or current general medical condition that might be impairing cognition or other psychiatric functioning * Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or HIV-1 and HIV-2. HCV antibody positive participants are eligible if HCV RNA is negative * Tardive dyskinesia that is moderate to severe or requires treatment * History of neuroleptic malignant syndrome * Average triplicate Fridericia's Correction Formula (QTcF) interval greater than 450 milliseconds (msec) for males and 470 msec for females or other clinically significant abnormality on screening electrocardiogram (ECG) based on centralized reading * Clinically significant abnormalities in laboratory safety test results * Significant or unstable physical condition that in the investigator's judgment might require a change in medication or hospitalization during the course of the study * On more than one antidepressant, or if on one antidepressant, a change in dose within 28 days prior to screening * History of clozapine treatment * History of treatment with electroconvulsive therapy (ECT) * Concomitant use of prohibited medications * Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenomorphine, methadone, cannabinoids, cocaine, and barbiturates * Receipt of an investigational drug within 28 days or five times the half-life of the investigational drug (whichever is longer) before the first study drug administration * Donation of blood over 400 mL within 3 months prior to screening * 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 |
|---|---|---|
| Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Baseline to Week 12 | The BNSS is a 13-item instrument designed for clinical trials that measures the severity of the negative symptoms of schizophrenia in five domains. There are 13 items organized into 6 subscales (anhedonia, distress, asociality, avolition, blunted affect, and alogia), each rated on a 7-point scale (0-6) where 0 = absent symptoms and 6 = severe symptoms. The total score is calculated by summing the individual items (13) of each subscale and has a range of 0-78. The avolition/apathy subscale contains 2 items with a total score range of 0-12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CGI-S Negative Symptoms (NS) Scores | Baseline to week 12 | The CGI-S-NS is similar to the CGI-S and is assessed on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). On the scale, the value 0 corresponds to 'not assessed', which will be excluded from the analyses. The values 1 to 7 will be transformed into the 0 to 6 range prior to statistical analysis for the question on the measure, making the total score range 0-6. |
| Clinical Global Impression - Improvement (CGI-I) Overall Scores | Up to Week 12 (Day 84) | The CGI-I assesses how much the participant's condition has changed at the time of the assessment in comparison to their condition at baseline. It uses a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), where the value 0 corresponds to 'not assessed' and will be excluded from any analyses. |
| CGI-I Negative Symptoms Scores | Up to Week 12 (Day 84) | The CGI-I NS is similar to the CGI-I and assesses how much the participant's condition has changed at the time of the assessment in comparison to their condition at baseline. It uses a 7-point scale, where: 1. = Very much improved 2. = Much improved 3. = Minimally improved 4. = No change 5. = Minimally worse 6. = Much worse 7. = Very much worse |
| Positive and Negative Syndrome Scale (PANSS) Total Scores | Baseline to week 12 | The PANSS Marder factors examine schizophrenia symptoms in five domains: positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and depression/anxiety. The Marder factor positive symptom score (range = 8-56) measures responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12) while the negative symptom factor score (range = 7-49) consists of 7 items (N1,N2,N3,N4,N6,G7,G16). Each item is scored on a scale of 1-7, where 1 = an absence of symptoms and 7 = extreme symptoms. The positive and negative syndrome scale total score is the sum of the scores from each domain (range = 15-105); higher scores indicate greater severity of symptoms. |
| PANSS Symptom Factor Scores | Baseline to week 12 | The PANSS Marder factors examine schizophrenia symptoms in five domains: positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and depression/anxiety. The Marder factor positive symptom score (range = 8-56) measures responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12) while the negative symptom factor score (range = 7-49) consists of 7 items (N1,N2,N3,N4,N6,G7,G16). Each item is scored on a scale of 1-7, where 1 = an absence of symptoms and 7 = extreme symptoms. |
| Clinical Global Impression Severity (CGI-S) Overall Scores | Baseline to week 12 | The CGI-S is an absolute measure assessing how mentally ill the participant is at the time of the assessment on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). On the scale, the value 0 corresponds to 'not assessed', which will be excluded from the analyses. The values 1 to 7 will be transformed into the 0 to 6 range prior to statistical analysis for the question on the measure (Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?), making the total score range 0-6. |
| Defeatist Performance Attitude Scale (DPAS) Scores | Baseline to week 12 | The DPAS is a 15-item, patient-rated assessment that evaluates expectations of failures or self-defeating beliefs related to prior failed experiences as well as illness on a 7-point Likert scale (total range = 15-105) ranging from totally agree (1) to totally disagree (7). |
| Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Baseline through Day 84 | The C-SSRS is a suicide risk assessment tool used to help identify the risk of suicide. |
| Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Baseline through Day 84 | The ESRS-A is used to evaluate the presence and severity of extrapyramidal symptoms. Items are rated on a scale of 0 (no symptoms) to 5 (extreme symptoms). |
| Maximum Serum Concentration (Cmax) of RO6889450 | Day 42 | — |
| Area Under the Curve at Steady State (AUCss) of RO6889450 | Day 42 | — |
| Brief Negative Symptom Scale (BNSS) Total Scores | Baseline to week 12 | The BNSS is a 13-item instrument designed for clinical trials that measures the severity of the negative symptoms of schizophrenia in five domains. There are 13 items organized into 6 subscales (anhedonia, distress, asociality, avolition, blunted affect, and alogia), each rated on a 7-point scale (0-6) where 0 = absent symptoms and 6 = severe symptoms. The total score is calculated by summing the individual items (13) of each subscale and has a range of 0-78. |
Countries
Japan, Spain, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: Monotherapy (Placebo) Participants received placebo each day (QD) for 12 weeks after a 1-week washout from their usual antipsychotic therapy. | 15 |
| Part A: Monotherapy (150 mg) Participants received 150 mg of ralmitaront QD for 12 weeks after a 1-week washout from their usual antipsychotic therapy. | 12 |
| Part B: Add-on Therapy (Placebo) Participants received placebo QD for 12 weeks in addition to their usual antipsychotic therapy. | 37 |
| Part B: Add-on Therapy (45 mg) Participants received 45 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (prior to protocol v5; arm was removed thereafter). | 5 |
| Part B: Add-on Therapy (150 mg) Participants received 150 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy. | 30 |
| Part B: Add-on Therapy (300 mg) Participants received 300 mg of ralmitaront QD 12 weeks in addition to their usual antipsychotic therapy (after protocol v5). | 32 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Disease Relapse | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | Part A: Monotherapy (Placebo) | Part A: Monotherapy (150 mg) | Part B: Add-on Therapy (Placebo) | Part B: Add-on Therapy (45 mg) | Part B: Add-on Therapy (150 mg) | Part B: Add-on Therapy (300 mg) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.7 Years STANDARD_DEVIATION 9.9 | 43.3 Years STANDARD_DEVIATION 6.6 | 41.3 Years STANDARD_DEVIATION 9.7 | 41.6 Years STANDARD_DEVIATION 11.3 | 40.0 Years STANDARD_DEVIATION 9.6 | 40.9 Years STANDARD_DEVIATION 9.2 | 41.3 Years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 6 Participants | 5 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 11 Participants | 35 Participants | 5 Participants | 24 Participants | 27 Participants | 116 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 8 Participants | 0 Participants | 6 Participants | 4 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 9 Participants | 11 Participants | 5 Participants | 7 Participants | 10 Participants | 54 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 16 Participants | 0 Participants | 16 Participants | 18 Participants | 55 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 10 Participants | 0 Participants | 11 Participants | 12 Participants | 39 Participants |
| Sex: Female, Male Male | 12 Participants | 9 Participants | 27 Participants | 5 Participants | 19 Participants | 20 Participants | 92 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 12 | 1 / 37 | 0 / 5 | 0 / 30 | 0 / 32 |
| other Total, other adverse events | 7 / 15 | 4 / 12 | 9 / 37 | 2 / 5 | 8 / 30 | 4 / 32 |
| serious Total, serious adverse events | 0 / 15 | 1 / 12 | 1 / 37 | 0 / 5 | 2 / 30 | 0 / 32 |
Outcome results
Primary
Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12
The BNSS is a 13-item instrument designed for clinical trials that measures the severity of the negative symptoms of schizophrenia in five domains. There are 13 items organized into 6 subscales (anhedonia, distress, asociality, avolition, blunted affect, and alogia), each rated on a 7-point scale (0-6) where 0 = absent symptoms and 6 = severe symptoms. The total score is calculated by summing the individual items (13) of each subscale and has a range of 0-78. The avolition/apathy subscale contains 2 items with a total score range of 0-12.
Time frame: Baseline to Week 12
Population: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Baseline Avolition/Apathy Subscore | 5.71 Units on a scale | Standard Deviation 2.81 |
| Part A: Monotherapy (Placebo) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Week 12 (Day 84) Avolition/Apathy Subscore | 5.50 Units on a scale | Standard Deviation 2.55 |
| Part A: Monotherapy (150 mg) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Baseline Avolition/Apathy Subscore | 5.50 Units on a scale | Standard Deviation 2.71 |
| Part A: Monotherapy (150 mg) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Week 12 (Day 84) Avolition/Apathy Subscore | 4.67 Units on a scale | Standard Deviation 3.27 |
| Part B: Add-on Therapy (Placebo) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Baseline Avolition/Apathy Subscore | 6.0 Units on a scale | Standard Deviation 2.3 |
| Part B: Add-on Therapy (Placebo) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Week 12 (Day 84) Avolition/Apathy Subscore | 5.0 Units on a scale | Standard Deviation 1.9 |
| Part B: Add-on Therapy (45 mg) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Baseline Avolition/Apathy Subscore | 6.2 Units on a scale | Standard Deviation 1.3 |
| Part B: Add-on Therapy (45 mg) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Week 12 (Day 84) Avolition/Apathy Subscore | 5.3 Units on a scale | Standard Deviation 1 |
| Part B: Add-on Therapy (150 mg) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Baseline Avolition/Apathy Subscore | 5.8 Units on a scale | Standard Deviation 1.9 |
| Part B: Add-on Therapy (150 mg) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Week 12 (Day 84) Avolition/Apathy Subscore | 4.1 Units on a scale | Standard Deviation 2.1 |
| Part B: Add-on Therapy (300 mg) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Baseline Avolition/Apathy Subscore | 5.9 Units on a scale | Standard Deviation 2.4 |
| Part B: Add-on Therapy (300 mg) | Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12 | Week 12 (Day 84) Avolition/Apathy Subscore | 4.7 Units on a scale | Standard Deviation 2.1 |
Secondary
Area Under the Curve at Steady State (AUCss) of RO6889450
Time frame: Day 42
Population: The pharmacokinetic population consisted of all participants who received at least one dose of study drug and who had data from at least one post-dose sample. It was pre-specified to not summarize and report Part A PK data, which was used only for model building.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Monotherapy (Placebo) | Area Under the Curve at Steady State (AUCss) of RO6889450 | 2980 h*ng/mL | Geometric Coefficient of Variation 54.8 |
| Part A: Monotherapy (150 mg) | Area Under the Curve at Steady State (AUCss) of RO6889450 | 15100 h*ng/mL | Geometric Coefficient of Variation 43.8 |
| Part B: Add-on Therapy (Placebo) | Area Under the Curve at Steady State (AUCss) of RO6889450 | 28600 h*ng/mL | Geometric Coefficient of Variation 48.4 |
Secondary
Brief Negative Symptom Scale (BNSS) Total Scores
The BNSS is a 13-item instrument designed for clinical trials that measures the severity of the negative symptoms of schizophrenia in five domains. There are 13 items organized into 6 subscales (anhedonia, distress, asociality, avolition, blunted affect, and alogia), each rated on a 7-point scale (0-6) where 0 = absent symptoms and 6 = severe symptoms. The total score is calculated by summing the individual items (13) of each subscale and has a range of 0-78.
Time frame: Baseline to week 12
Population: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 84 (Week 12) | 30.40 Units on a scale | Standard Deviation 12.86 |
| Part A: Monotherapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 42 | 34.09 Units on a scale | Standard Deviation 11.95 |
| Part A: Monotherapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 28 | 29.90 Units on a scale | Standard Deviation 14.49 |
| Part A: Monotherapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 70 | 33.10 Units on a scale | Standard Deviation 7.23 |
| Part A: Monotherapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 56 | 37.40 Units on a scale | Standard Deviation 18.6 |
| Part A: Monotherapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Baseline | 34.79 Units on a scale | Standard Deviation 14.98 |
| Part A: Monotherapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 14 | 35.08 Units on a scale | Standard Deviation 12.48 |
| Part A: Monotherapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 42 | 36.38 Units on a scale | Standard Deviation 14.79 |
| Part A: Monotherapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Baseline | 35.17 Units on a scale | Standard Deviation 13.68 |
| Part A: Monotherapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 14 | 32.90 Units on a scale | Standard Deviation 13.47 |
| Part A: Monotherapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 28 | 33.25 Units on a scale | Standard Deviation 8.94 |
| Part A: Monotherapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 56 | 34.00 Units on a scale | Standard Deviation 12.12 |
| Part A: Monotherapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 70 | 34.00 Units on a scale | Standard Deviation 15.15 |
| Part A: Monotherapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 84 (Week 12) | 28.17 Units on a scale | Standard Deviation 20.44 |
| Part B: Add-on Therapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 84 (Week 12) | 32.7 Units on a scale | Standard Deviation 13.4 |
| Part B: Add-on Therapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 14 | 36.1 Units on a scale | Standard Deviation 11.4 |
| Part B: Add-on Therapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 42 | 35.1 Units on a scale | Standard Deviation 11.3 |
| Part B: Add-on Therapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 56 | 30.3 Units on a scale | Standard Deviation 12.1 |
| Part B: Add-on Therapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Baseline | 36.6 Units on a scale | Standard Deviation 14.9 |
| Part B: Add-on Therapy (Placebo) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 28 | 32.6 Units on a scale | Standard Deviation 12.9 |
| Part B: Add-on Therapy (45 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 84 (Week 12) | 33.3 Units on a scale | Standard Deviation 10.6 |
| Part B: Add-on Therapy (45 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 56 | 37.5 Units on a scale | Standard Deviation 16.3 |
| Part B: Add-on Therapy (45 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 28 | 32.7 Units on a scale | Standard Deviation 7.4 |
| Part B: Add-on Therapy (45 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 42 | 35.0 Units on a scale | Standard Deviation 11.8 |
| Part B: Add-on Therapy (45 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Baseline | 36.4 Units on a scale | Standard Deviation 6.7 |
| Part B: Add-on Therapy (45 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 14 | 29.3 Units on a scale | Standard Deviation 11.1 |
| Part B: Add-on Therapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 84 (Week 12) | 29.6 Units on a scale | Standard Deviation 9.2 |
| Part B: Add-on Therapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 28 | 33.1 Units on a scale | Standard Deviation 13.4 |
| Part B: Add-on Therapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Baseline | 38.1 Units on a scale | Standard Deviation 13.7 |
| Part B: Add-on Therapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 14 | 34.1 Units on a scale | Standard Deviation 12.8 |
| Part B: Add-on Therapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 42 | 35.5 Units on a scale | Standard Deviation 12.6 |
| Part B: Add-on Therapy (150 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 56 | 30.8 Units on a scale | Standard Deviation 11.8 |
| Part B: Add-on Therapy (300 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Baseline | 38.4 Units on a scale | Standard Deviation 13.8 |
| Part B: Add-on Therapy (300 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 42 | 32.7 Units on a scale | Standard Deviation 13.4 |
| Part B: Add-on Therapy (300 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 14 | 35.2 Units on a scale | Standard Deviation 12.8 |
| Part B: Add-on Therapy (300 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 56 | 32.3 Units on a scale | Standard Deviation 13.6 |
| Part B: Add-on Therapy (300 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 28 | 36.5 Units on a scale | Standard Deviation 10.3 |
| Part B: Add-on Therapy (300 mg) | Brief Negative Symptom Scale (BNSS) Total Scores | Day 84 (Week 12) | 29.2 Units on a scale | Standard Deviation 12.4 |
Secondary
CGI-I Negative Symptoms Scores
The CGI-I NS is similar to the CGI-I and assesses how much the participant's condition has changed at the time of the assessment in comparison to their condition at baseline. It uses a 7-point scale, where: 1. = Very much improved 2. = Much improved 3. = Minimally improved 4. = No change 5. = Minimally worse 6. = Much worse 7. = Very much worse
Time frame: Up to Week 12 (Day 84)
Population: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | CGI-I Negative Symptoms Scores | Day 42 | 3.45 Units on a scale | Standard Deviation 0.69 |
| Part A: Monotherapy (Placebo) | CGI-I Negative Symptoms Scores | Day 28 | 3.44 Units on a scale | Standard Deviation 0.73 |
| Part A: Monotherapy (Placebo) | CGI-I Negative Symptoms Scores | Day 14 | 3.71 Units on a scale | Standard Deviation 0.61 |
| Part A: Monotherapy (Placebo) | CGI-I Negative Symptoms Scores | Day 35 | 4.50 Units on a scale | Standard Deviation 0.71 |
| Part A: Monotherapy (Placebo) | CGI-I Negative Symptoms Scores | Day 21 | 5.00 Units on a scale | — |
| Part A: Monotherapy (Placebo) | CGI-I Negative Symptoms Scores | Day 84 | 3.10 Units on a scale | Standard Deviation 0.74 |
| Part A: Monotherapy (Placebo) | CGI-I Negative Symptoms Scores | Day 56 | 3.50 Units on a scale | Standard Deviation 0.71 |
| Part A: Monotherapy (Placebo) | CGI-I Negative Symptoms Scores | Day 70 | 3.40 Units on a scale | Standard Deviation 0.7 |
| Part A: Monotherapy (150 mg) | CGI-I Negative Symptoms Scores | Day 42 | 3.43 Units on a scale | Standard Deviation 0.79 |
| Part A: Monotherapy (150 mg) | CGI-I Negative Symptoms Scores | Day 21 | 4.00 Units on a scale | — |
| Part A: Monotherapy (150 mg) | CGI-I Negative Symptoms Scores | Day 14 | 3.44 Units on a scale | Standard Deviation 0.73 |
| Part A: Monotherapy (150 mg) | CGI-I Negative Symptoms Scores | Day 28 | 3.38 Units on a scale | Standard Deviation 0.74 |
| Part A: Monotherapy (150 mg) | CGI-I Negative Symptoms Scores | Day 56 | 3.43 Units on a scale | Standard Deviation 0.53 |
| Part A: Monotherapy (150 mg) | CGI-I Negative Symptoms Scores | Day 70 | 3.00 Units on a scale | Standard Deviation 0.82 |
| Part A: Monotherapy (150 mg) | CGI-I Negative Symptoms Scores | Day 84 | 2.83 Units on a scale | Standard Deviation 0.41 |
| Part B: Add-on Therapy (Placebo) | CGI-I Negative Symptoms Scores | Day 28 | 3.5 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (Placebo) | CGI-I Negative Symptoms Scores | Day 56 | 3.2 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (Placebo) | CGI-I Negative Symptoms Scores | Day 14 | 3.7 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (Placebo) | CGI-I Negative Symptoms Scores | Day 42 | 3.3 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (Placebo) | CGI-I Negative Symptoms Scores | Day 84 | 3.1 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (45 mg) | CGI-I Negative Symptoms Scores | Day 56 | 3.5 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (45 mg) | CGI-I Negative Symptoms Scores | Day 42 | 3.5 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (45 mg) | CGI-I Negative Symptoms Scores | Day 14 | 4.0 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (45 mg) | CGI-I Negative Symptoms Scores | Day 84 | 3.0 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (45 mg) | CGI-I Negative Symptoms Scores | Day 28 | 4.0 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (150 mg) | CGI-I Negative Symptoms Scores | Day 56 | 3.2 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (150 mg) | CGI-I Negative Symptoms Scores | Day 84 | 2.9 Units on a scale | Standard Deviation 0.9 |
| Part B: Add-on Therapy (150 mg) | CGI-I Negative Symptoms Scores | Day 14 | 3.5 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (150 mg) | CGI-I Negative Symptoms Scores | Day 28 | 3.3 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (150 mg) | CGI-I Negative Symptoms Scores | Day 42 | 3.3 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (300 mg) | CGI-I Negative Symptoms Scores | Day 42 | 3.2 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (300 mg) | CGI-I Negative Symptoms Scores | Day 56 | 2.9 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (300 mg) | CGI-I Negative Symptoms Scores | Day 84 | 2.8 Units on a scale | Standard Deviation 0.9 |
| Part B: Add-on Therapy (300 mg) | CGI-I Negative Symptoms Scores | Day 14 | 3.5 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (300 mg) | CGI-I Negative Symptoms Scores | Day 28 | 3.2 Units on a scale | Standard Deviation 0.8 |
Secondary
CGI-S Negative Symptoms (NS) Scores
The CGI-S-NS is similar to the CGI-S and is assessed on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). On the scale, the value 0 corresponds to 'not assessed', which will be excluded from the analyses. The values 1 to 7 will be transformed into the 0 to 6 range prior to statistical analysis for the question on the measure, making the total score range 0-6.
Time frame: Baseline to week 12
Population: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug. Data for this endpoint was not collected for Part B on Day 70.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 28 | 3.800 Units on a scale | Standard Deviation 0.632 |
| Part A: Monotherapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 42 | 3.727 Units on a scale | Standard Deviation 0.467 |
| Part A: Monotherapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 84 | 3.400 Units on a scale | Standard Deviation 0.516 |
| Part A: Monotherapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 70 | 3.500 Units on a scale | Standard Deviation 0.527 |
| Part A: Monotherapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 14 | 3.600 Units on a scale | Standard Deviation 0.632 |
| Part A: Monotherapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Baseline | 3.867 Units on a scale | Standard Deviation 0.743 |
| Part A: Monotherapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 56 | 3.636 Units on a scale | Standard Deviation 0.674 |
| Part A: Monotherapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 42 | 3.625 Units on a scale | Standard Deviation 0.518 |
| Part A: Monotherapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 28 | 3.778 Units on a scale | Standard Deviation 0.667 |
| Part A: Monotherapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 56 | 3.714 Units on a scale | Standard Deviation 0.756 |
| Part A: Monotherapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Baseline | 3.917 Units on a scale | Standard Deviation 0.669 |
| Part A: Monotherapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 84 | 3.167 Units on a scale | Standard Deviation 0.753 |
| Part A: Monotherapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 14 | 3.800 Units on a scale | Standard Deviation 0.632 |
| Part A: Monotherapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 70 | 3.286 Units on a scale | Standard Deviation 0.756 |
| Part B: Add-on Therapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 28 | 4.1 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Baseline | 4.4 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 14 | 4.3 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 42 | 3.9 Units on a scale | Standard Deviation 0.9 |
| Part B: Add-on Therapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 56 | 3.9 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (Placebo) | CGI-S Negative Symptoms (NS) Scores | Day 84 | 3.9 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (45 mg) | CGI-S Negative Symptoms (NS) Scores | Day 14 | 4.3 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (45 mg) | CGI-S Negative Symptoms (NS) Scores | Day 56 | 4.0 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (45 mg) | CGI-S Negative Symptoms (NS) Scores | Day 28 | 4.3 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (45 mg) | CGI-S Negative Symptoms (NS) Scores | Day 84 | 3.8 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (45 mg) | CGI-S Negative Symptoms (NS) Scores | Day 42 | 4.0 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (45 mg) | CGI-S Negative Symptoms (NS) Scores | Baseline | 4.2 Units on a scale | Standard Deviation 0.4 |
| Part B: Add-on Therapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Baseline | 4.3 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 14 | 3.9 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 28 | 3.8 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 84 | 3.4 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 56 | 3.6 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (150 mg) | CGI-S Negative Symptoms (NS) Scores | Day 42 | 3.8 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (300 mg) | CGI-S Negative Symptoms (NS) Scores | Day 14 | 4.1 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (300 mg) | CGI-S Negative Symptoms (NS) Scores | Day 42 | 3.7 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (300 mg) | CGI-S Negative Symptoms (NS) Scores | Day 56 | 3.5 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (300 mg) | CGI-S Negative Symptoms (NS) Scores | Baseline | 4.3 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (300 mg) | CGI-S Negative Symptoms (NS) Scores | Day 84 | 3.5 Units on a scale | Standard Deviation 0.9 |
| Part B: Add-on Therapy (300 mg) | CGI-S Negative Symptoms (NS) Scores | Day 28 | 3.9 Units on a scale | Standard Deviation 0.7 |
Secondary
Clinical Global Impression - Improvement (CGI-I) Overall Scores
The CGI-I assesses how much the participant's condition has changed at the time of the assessment in comparison to their condition at baseline. It uses a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), where the value 0 corresponds to 'not assessed' and will be excluded from any analyses.
Time frame: Up to Week 12 (Day 84)
Population: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug. Data for this endpoint was not collected for Part B Days 21, 35, and 70.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 42 | 3.73 Units on a scale | Standard Deviation 0.65 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 14 | 3.71 Units on a scale | Standard Deviation 0.91 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 84 | 3.80 Units on a scale | Standard Deviation 0.42 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 21 | 4.00 Units on a scale | — |
| Part A: Monotherapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 28 | 3.56 Units on a scale | Standard Deviation 0.73 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 70 | 3.50 Units on a scale | Standard Deviation 0.71 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 56 | 3.70 Units on a scale | Standard Deviation 0.48 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 35 | 3.50 Units on a scale | Standard Deviation 0.71 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 42 | 3.29 Units on a scale | Standard Deviation 0.76 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 56 | 3.14 Units on a scale | Standard Deviation 0.69 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 84 | 3.00 Units on a scale | Standard Deviation 0.63 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 28 | 3.50 Units on a scale | Standard Deviation 0.76 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 70 | 2.86 Units on a scale | Standard Deviation 0.9 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 14 | 3.56 Units on a scale | Standard Deviation 0.53 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 21 | 2.00 Units on a scale | — |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 42 | 3.4 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 14 | 3.7 Units on a scale | Standard Deviation 0.4 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 28 | 3.5 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 56 | 3.4 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 84 | 3.2 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 42 | 3.8 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 84 | 3.8 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 28 | 4.0 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 14 | 4.0 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 56 | 3.8 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 42 | 3.3 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 28 | 3.5 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 84 | 3.0 Units on a scale | Standard Deviation 0.9 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 56 | 3.4 Units on a scale | Standard Deviation 0.9 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 14 | 3.6 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 14 | 3.6 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 84 | 3.0 Units on a scale | Standard Deviation 1 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 56 | 3.1 Units on a scale | Standard Deviation 1 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 28 | 3.4 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression - Improvement (CGI-I) Overall Scores | Day 42 | 3.3 Units on a scale | Standard Deviation 0.9 |
Secondary
Clinical Global Impression Severity (CGI-S) Overall Scores
The CGI-S is an absolute measure assessing how mentally ill the participant is at the time of the assessment on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). On the scale, the value 0 corresponds to 'not assessed', which will be excluded from the analyses. The values 1 to 7 will be transformed into the 0 to 6 range prior to statistical analysis for the question on the measure (Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?), making the total score range 0-6.
Time frame: Baseline to week 12
Population: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug. Data for this endpoint was not collected for Part B on Day 70.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 56 | 3.636 Units on a scale | Standard Deviation 0.505 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 28 | 3.500 Units on a scale | Standard Deviation 0.527 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 42 | 3.636 Units on a scale | Standard Deviation 0.809 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 14 | 3.467 Units on a scale | Standard Deviation 0.516 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 84 | 3.700 Units on a scale | Standard Deviation 0.483 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 70 | 3.500 Units on a scale | Standard Deviation 0.707 |
| Part A: Monotherapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Baseline | 3.600 Units on a scale | Standard Deviation 0.507 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 70 | 3.143 Units on a scale | Standard Deviation 0.69 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 28 | 3.333 Units on a scale | Standard Deviation 0.5 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Baseline | 3.667 Units on a scale | Standard Deviation 0.492 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 56 | 3.143 Units on a scale | Standard Deviation 0.378 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 42 | 3.375 Units on a scale | Standard Deviation 0.744 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 84 | 3.000 Units on a scale | Standard Deviation 0.632 |
| Part A: Monotherapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 14 | 3.700 Units on a scale | Standard Deviation 0.483 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 28 | 3.9 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 56 | 3.8 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Baseline | 4.1 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 14 | 4.0 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 84 | 3.7 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (Placebo) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 42 | 3.8 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 14 | 3.8 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 84 | 3.8 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Baseline | 3.8 Units on a scale | Standard Deviation 0.4 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 56 | 3.8 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 42 | 3.8 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (45 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 28 | 3.8 Units on a scale | Standard Deviation 0.5 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 28 | 3.8 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Baseline | 3.9 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 14 | 3.8 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 42 | 3.6 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 56 | 3.5 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (150 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 84 | 3.4 Units on a scale | Standard Deviation 0.6 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 42 | 3.6 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 28 | 3.7 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 14 | 4.0 Units on a scale | Standard Deviation 0.8 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Baseline | 4.0 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 84 | 3.5 Units on a scale | Standard Deviation 0.7 |
| Part B: Add-on Therapy (300 mg) | Clinical Global Impression Severity (CGI-S) Overall Scores | Day 56 | 3.5 Units on a scale | Standard Deviation 0.8 |
Secondary
Defeatist Performance Attitude Scale (DPAS) Scores
The DPAS is a 15-item, patient-rated assessment that evaluates expectations of failures or self-defeating beliefs related to prior failed experiences as well as illness on a 7-point Likert scale (total range = 15-105) ranging from totally agree (1) to totally disagree (7).
Time frame: Baseline to week 12
Population: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 42 | 40.54 Units on a scale | Standard Deviation 16.37 |
| Part A: Monotherapy (Placebo) | Defeatist Performance Attitude Scale (DPAS) Scores | Baseline | 34.73 Units on a scale | Standard Deviation 13.92 |
| Part A: Monotherapy (Placebo) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 84 (Week 12) | 38.80 Units on a scale | Standard Deviation 13.42 |
| Part A: Monotherapy (150 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 42 | 27.50 Units on a scale | Standard Deviation 18.65 |
| Part A: Monotherapy (150 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Baseline | 30.25 Units on a scale | Standard Deviation 12.43 |
| Part A: Monotherapy (150 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 84 (Week 12) | 16.00 Units on a scale | Standard Deviation 4.98 |
| Part B: Add-on Therapy (Placebo) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 42 | 37.5 Units on a scale | Standard Deviation 14.2 |
| Part B: Add-on Therapy (Placebo) | Defeatist Performance Attitude Scale (DPAS) Scores | Baseline | 40.2 Units on a scale | Standard Deviation 14.6 |
| Part B: Add-on Therapy (Placebo) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 84 (Week 12) | 36.0 Units on a scale | Standard Deviation 15.2 |
| Part B: Add-on Therapy (45 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 42 | 39.3 Units on a scale | Standard Deviation 9.3 |
| Part B: Add-on Therapy (45 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Baseline | 40.0 Units on a scale | Standard Deviation 6.4 |
| Part B: Add-on Therapy (45 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 84 (Week 12) | 54.3 Units on a scale | Standard Deviation 16.4 |
| Part B: Add-on Therapy (150 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 42 | 38.8 Units on a scale | Standard Deviation 16.2 |
| Part B: Add-on Therapy (150 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Baseline | 38.2 Units on a scale | Standard Deviation 15.9 |
| Part B: Add-on Therapy (150 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 84 (Week 12) | 39.0 Units on a scale | Standard Deviation 19.9 |
| Part B: Add-on Therapy (300 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Baseline | 35.9 Units on a scale | Standard Deviation 16.2 |
| Part B: Add-on Therapy (300 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 84 (Week 12) | 32.2 Units on a scale | Standard Deviation 13.6 |
| Part B: Add-on Therapy (300 mg) | Defeatist Performance Attitude Scale (DPAS) Scores | Day 42 | 36.0 Units on a scale | Standard Deviation 16.2 |
Secondary
Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A)
The ESRS-A is used to evaluate the presence and severity of extrapyramidal symptoms. Items are rated on a scale of 0 (no symptoms) to 5 (extreme symptoms).
Time frame: Baseline through Day 84
Population: The safety population included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Baseline | 0.07 Units on a scale | Standard Deviation 0.26 |
| Part A: Monotherapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Day 84 | 0.00 Units on a scale | Standard Deviation 0 |
| Part A: Monotherapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Baseline | 0.00 Units on a scale | Standard Deviation 0 |
| Part A: Monotherapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Day 84 | 0.20 Units on a scale | Standard Deviation 0.63 |
| Part A: Monotherapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Baseline | 0.13 Units on a scale | Standard Deviation 0.52 |
| Part A: Monotherapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Day 84 | 0.10 Units on a scale | Standard Deviation 0.32 |
| Part A: Monotherapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Baseline | 0.07 Units on a scale | Standard Deviation 0.26 |
| Part A: Monotherapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Day 84 | 0.00 Units on a scale | Standard Deviation 0 |
| Part A: Monotherapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Baseline | 0.42 Units on a scale | Standard Deviation 1 |
| Part A: Monotherapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Baseline | 0.00 Units on a scale | Standard Deviation 0 |
| Part A: Monotherapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Baseline | 0.08 Units on a scale | Standard Deviation 0.29 |
| Part A: Monotherapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Baseline | 0.33 Units on a scale | Standard Deviation 0.89 |
| Part A: Monotherapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Day 84 | 0.00 Units on a scale | Standard Deviation 0 |
| Part A: Monotherapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Day 84 | 0.00 Units on a scale | Standard Deviation 0 |
| Part A: Monotherapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Day 84 | 0.33 Units on a scale | Standard Deviation 0.82 |
| Part A: Monotherapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Day 84 | 0.00 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Day 84 | 1.03 Units on a scale | Standard Deviation 2.87 |
| Part B: Add-on Therapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Day 84 | 0.29 Units on a scale | Standard Deviation 0.94 |
| Part B: Add-on Therapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Baseline | 0.46 Units on a scale | Standard Deviation 1.95 |
| Part B: Add-on Therapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Day 84 | 0.16 Units on a scale | Standard Deviation 0.9 |
| Part B: Add-on Therapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Baseline | 0.24 Units on a scale | Standard Deviation 0.86 |
| Part B: Add-on Therapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Baseline | 1.03 Units on a scale | Standard Deviation 2.36 |
| Part B: Add-on Therapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Day 84 | 0.26 Units on a scale | Standard Deviation 1.03 |
| Part B: Add-on Therapy (Placebo) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Baseline | 0.27 Units on a scale | Standard Deviation 0.87 |
| Part B: Add-on Therapy (45 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Baseline | 2.20 Units on a scale | Standard Deviation 1.92 |
| Part B: Add-on Therapy (45 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Day 84 | 0.33 Units on a scale | Standard Deviation 0.58 |
| Part B: Add-on Therapy (45 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Day 84 | 0.00 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (45 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Baseline | 0.75 Units on a scale | Standard Deviation 0.96 |
| Part B: Add-on Therapy (45 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Day 84 | 0.00 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (45 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Baseline | 0.00 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (45 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Baseline | 0.00 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (45 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Day 84 | 0.00 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Baseline | 0.03 Units on a scale | Standard Deviation 0.18 |
| Part B: Add-on Therapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Baseline | 2.00 Units on a scale | Standard Deviation 3.24 |
| Part B: Add-on Therapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Day 84 | 0.05 Units on a scale | Standard Deviation 0.22 |
| Part B: Add-on Therapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Day 84 | 0.15 Units on a scale | Standard Deviation 0.49 |
| Part B: Add-on Therapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Baseline | 0.17 Units on a scale | Standard Deviation 0.38 |
| Part B: Add-on Therapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Day 84 | 0.10 Units on a scale | Standard Deviation 0.45 |
| Part B: Add-on Therapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Day 84 | 1.15 Units on a scale | Standard Deviation 2.68 |
| Part B: Add-on Therapy (150 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Baseline | 0.27 Units on a scale | Standard Deviation 0.83 |
| Part B: Add-on Therapy (300 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Day 84 | 1.00 Units on a scale | Standard Deviation 2.3 |
| Part B: Add-on Therapy (300 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Baseline | 0.38 Units on a scale | Standard Deviation 0.98 |
| Part B: Add-on Therapy (300 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Akathisia Day 84 | 0.10 Units on a scale | Standard Deviation 0.44 |
| Part B: Add-on Therapy (300 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Baseline | 0.63 Units on a scale | Standard Deviation 1.68 |
| Part B: Add-on Therapy (300 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dyskinesia Day 84 | 0.29 Units on a scale | Standard Deviation 0.72 |
| Part B: Add-on Therapy (300 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Baseline | 0.16 Units on a scale | Standard Deviation 0.51 |
| Part B: Add-on Therapy (300 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Dystonia Day 84 | 0.00 Units on a scale | Standard Deviation 0 |
| Part B: Add-on Therapy (300 mg) | Extrapyramidal Symptom Rating Scale, Abbreviated (ESRS-A) | Parkinsonism Baseline | 2.22 Units on a scale | Standard Deviation 4.15 |
Secondary
Maximum Serum Concentration (Cmax) of RO6889450
Time frame: Day 42
Population: The pharmacokinetic population consisted of all participants who received at least one dose of study drug and who had data from at least one post-dose sample. It was pre-specified to not summarize and report Part A PK data, which was used only for model building.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Monotherapy (Placebo) | Maximum Serum Concentration (Cmax) of RO6889450 | 157 ng/mL | Geometric Coefficient of Variation 58.7 |
| Part A: Monotherapy (150 mg) | Maximum Serum Concentration (Cmax) of RO6889450 | 794 ng/mL | Geometric Coefficient of Variation 40.3 |
| Part B: Add-on Therapy (Placebo) | Maximum Serum Concentration (Cmax) of RO6889450 | 1550 ng/mL | Geometric Coefficient of Variation 43.9 |
Secondary
Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is a suicide risk assessment tool used to help identify the risk of suicide.
Time frame: Baseline through Day 84
Population: The safety population included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Monotherapy (Placebo) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation or behavior | 0 Number of participants |
| Part A: Monotherapy (Placebo) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious behavior without suicidal intent | 1 Number of participants |
| Part A: Monotherapy (150 mg) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation or behavior | 0 Number of participants |
| Part A: Monotherapy (150 mg) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious behavior without suicidal intent | 0 Number of participants |
| Part B: Add-on Therapy (Placebo) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation or behavior | 1 Number of participants |
| Part B: Add-on Therapy (Placebo) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious behavior without suicidal intent | 0 Number of participants |
| Part B: Add-on Therapy (45 mg) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation or behavior | 0 Number of participants |
| Part B: Add-on Therapy (45 mg) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious behavior without suicidal intent | 0 Number of participants |
| Part B: Add-on Therapy (150 mg) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation or behavior | 2 Number of participants |
| Part B: Add-on Therapy (150 mg) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious behavior without suicidal intent | 0 Number of participants |
| Part B: Add-on Therapy (300 mg) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Suicidal ideation or behavior | 1 Number of participants |
| Part B: Add-on Therapy (300 mg) | Number of Participants With Suicidal Ideation or Behavior, and Self-injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) | Self-injurious behavior without suicidal intent | 0 Number of participants |
Secondary
PANSS Symptom Factor Scores
The PANSS Marder factors examine schizophrenia symptoms in five domains: positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and depression/anxiety. The Marder factor positive symptom score (range = 8-56) measures responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12) while the negative symptom factor score (range = 7-49) consists of 7 items (N1,N2,N3,N4,N6,G7,G16). Each item is scored on a scale of 1-7, where 1 = an absence of symptoms and 7 = extreme symptoms.
Time frame: Baseline to week 12
Population: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 14 - Positive symptoms | 18.23 Units on a scale | Standard Deviation 4.75 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 70 - Negative symptoms | 21.20 Units on a scale | Standard Deviation 5.07 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Negative symptoms | 18.90 Units on a scale | Standard Deviation 5.38 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 28 - Positive symptoms | 17.60 Units on a scale | Standard Deviation 4.77 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Baseline - Positive symptoms | 17.93 Units on a scale | Standard Deviation 3.99 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Baseline - Negative symptoms | 21.29 Units on a scale | Standard Deviation 4.45 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Positive symptoms | 17.70 Units on a scale | Standard Deviation 5.25 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 14 - Negative symptoms | 22.46 Units on a scale | Standard Deviation 5.13 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 70 - Positive symptoms | 19.20 Units on a scale | Standard Deviation 2.86 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 28 - Negative symptoms | 18.40 Units on a scale | Standard Deviation 6.67 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 56 - Positive symptoms | 17.90 Units on a scale | Standard Deviation 4.93 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 42 - Negative symptoms | 21.09 Units on a scale | Standard Deviation 5.45 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 56 - Negative symptoms | 21.10 Units on a scale | Standard Deviation 5.93 |
| Part A: Monotherapy (Placebo) | PANSS Symptom Factor Scores | Day 42 - Positive symptoms | 17.82 Units on a scale | Standard Deviation 4.31 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 14 - Positive symptoms | 21.30 Units on a scale | Standard Deviation 4.35 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 70 - Positive symptoms | 19.29 Units on a scale | Standard Deviation 2.69 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 42 - Positive symptoms | 18.75 Units on a scale | Standard Deviation 4.13 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 14 - Negative symptoms | 20.40 Units on a scale | Standard Deviation 3.95 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Baseline - Positive symptoms | 19.75 Units on a scale | Standard Deviation 3.93 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Positive symptoms | 19.67 Units on a scale | Standard Deviation 3.61 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 28 - Negative symptoms | 20.44 Units on a scale | Standard Deviation 3.68 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 56 - Positive symptoms | 20.71 Units on a scale | Standard Deviation 1.5 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 70 - Negative symptoms | 17.71 Units on a scale | Standard Deviation 2.75 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 56 - Negative symptoms | 18.71 Units on a scale | Standard Deviation 4.72 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Negative symptoms | 15.33 Units on a scale | Standard Deviation 3.08 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 42 - Negative symptoms | 19.00 Units on a scale | Standard Deviation 5.5 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Day 28 - Positive symptoms | 19.22 Units on a scale | Standard Deviation 5.19 |
| Part A: Monotherapy (150 mg) | PANSS Symptom Factor Scores | Baseline - Negative symptoms | 21.00 Units on a scale | Standard Deviation 5.2 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 42 - Positive symptoms | 18.2 Units on a scale | Standard Deviation 4.8 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Baseline - Negative symptoms | 23.0 Units on a scale | Standard Deviation 4.7 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 28 - Positive symptoms | 17.9 Units on a scale | Standard Deviation 4.3 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 14 - Negative symptoms | 22.9 Units on a scale | Standard Deviation 3.4 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 14 - Positive symptoms | 17.8 Units on a scale | Standard Deviation 3.8 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 42 - Negative symptoms | 21.3 Units on a scale | Standard Deviation 4.5 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 56 - Positive symptoms | 17.7 Units on a scale | Standard Deviation 5 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Negative symptoms | 20.5 Units on a scale | Standard Deviation 5.9 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 56 - Negative symptoms | 20.4 Units on a scale | Standard Deviation 4.7 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 28 - Negative symptoms | 20.9 Units on a scale | Standard Deviation 4.8 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Baseline - Positive symptoms | 18.9 Units on a scale | Standard Deviation 4.6 |
| Part B: Add-on Therapy (Placebo) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Positive symptoms | 17.3 Units on a scale | Standard Deviation 4.5 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 56 - Positive symptoms | 20.5 Units on a scale | Standard Deviation 3.1 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 14 - Positive symptoms | 18.3 Units on a scale | Standard Deviation 5.3 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Baseline - Negative symptoms | 20.6 Units on a scale | Standard Deviation 3.3 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 14 - Negative symptoms | 20.8 Units on a scale | Standard Deviation 2.9 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 28 - Negative symptoms | 20.3 Units on a scale | Standard Deviation 3.1 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 42 - Negative symptoms | 22.3 Units on a scale | Standard Deviation 3.2 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 56 - Negative symptoms | 21.8 Units on a scale | Standard Deviation 4.2 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Negative symptoms | 22.5 Units on a scale | Standard Deviation 4.8 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Baseline - Positive symptoms | 18.0 Units on a scale | Standard Deviation 3.7 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 28 - Positive symptoms | 24.3 Units on a scale | Standard Deviation 6 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 42 - Positive symptoms | 22.5 Units on a scale | Standard Deviation 6 |
| Part B: Add-on Therapy (45 mg) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Positive symptoms | 21.5 Units on a scale | Standard Deviation 2.6 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 28 - Negative symptoms | 21.5 Units on a scale | Standard Deviation 4 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 28 - Positive symptoms | 18.0 Units on a scale | Standard Deviation 4.9 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 14 - Negative symptoms | 21.8 Units on a scale | Standard Deviation 4.5 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 56 - Positive symptoms | 17.2 Units on a scale | Standard Deviation 6.1 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 42 - Negative symptoms | 21.5 Units on a scale | Standard Deviation 5.1 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Negative symptoms | 18.6 Units on a scale | Standard Deviation 4.4 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Positive symptoms | 16.5 Units on a scale | Standard Deviation 4.7 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Baseline - Negative symptoms | 23.3 Units on a scale | Standard Deviation 4.7 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 42 - Positive symptoms | 16.0 Units on a scale | Standard Deviation 4.4 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 14 - Positive symptoms | 18.1 Units on a scale | Standard Deviation 3.9 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Baseline - Positive symptoms | 17.6 Units on a scale | Standard Deviation 4.2 |
| Part B: Add-on Therapy (150 mg) | PANSS Symptom Factor Scores | Day 56 - Negative symptoms | 19.8 Units on a scale | Standard Deviation 4.9 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Baseline - Positive symptoms | 17.2 Units on a scale | Standard Deviation 5.4 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Positive symptoms | 15.5 Units on a scale | Standard Deviation 4.3 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 28 - Positive symptoms | 17.4 Units on a scale | Standard Deviation 5.9 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 42 - Negative symptoms | 20.7 Units on a scale | Standard Deviation 5.1 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 42 - Positive symptoms | 16.2 Units on a scale | Standard Deviation 4.7 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 28 - Negative symptoms | 22.1 Units on a scale | Standard Deviation 4.9 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 14 - Negative symptoms | 22.2 Units on a scale | Standard Deviation 5.3 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 56 - Positive symptoms | 15.8 Units on a scale | Standard Deviation 4.5 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Baseline - Negative symptoms | 23.5 Units on a scale | Standard Deviation 4.1 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 84 (Week 12) - Negative symptoms | 19.4 Units on a scale | Standard Deviation 4.8 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 14 - Positive symptoms | 18.0 Units on a scale | Standard Deviation 5.7 |
| Part B: Add-on Therapy (300 mg) | PANSS Symptom Factor Scores | Day 56 - Negative symptoms | 20.3 Units on a scale | Standard Deviation 5.7 |
Secondary
Positive and Negative Syndrome Scale (PANSS) Total Scores
The PANSS Marder factors examine schizophrenia symptoms in five domains: positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and depression/anxiety. The Marder factor positive symptom score (range = 8-56) measures responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12) while the negative symptom factor score (range = 7-49) consists of 7 items (N1,N2,N3,N4,N6,G7,G16). Each item is scored on a scale of 1-7, where 1 = an absence of symptoms and 7 = extreme symptoms. The positive and negative syndrome scale total score is the sum of the scores from each domain (range = 15-105); higher scores indicate greater severity of symptoms.
Time frame: Baseline to week 12
Population: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Monotherapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 14 | 68.38 Units on a scale | Standard Deviation 10.37 |
| Part A: Monotherapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 56 | 66.60 Units on a scale | Standard Deviation 8.13 |
| Part A: Monotherapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 28 | 66.10 Units on a scale | Standard Deviation 10.38 |
| Part A: Monotherapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Baseline | 67.43 Units on a scale | Standard Deviation 9.35 |
| Part A: Monotherapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 84 (Week 12) | 64.70 Units on a scale | Standard Deviation 13.92 |
| Part A: Monotherapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 70 | 68.50 Units on a scale | Standard Deviation 7.65 |
| Part A: Monotherapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 42 | 70.09 Units on a scale | Standard Deviation 10.88 |
| Part A: Monotherapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Baseline | 67.92 Units on a scale | Standard Deviation 10.86 |
| Part A: Monotherapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 56 | 61.14 Units on a scale | Standard Deviation 6.91 |
| Part A: Monotherapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 84 (Week 12) | 59.17 Units on a scale | Standard Deviation 6.27 |
| Part A: Monotherapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 14 | 69.00 Units on a scale | Standard Deviation 11.4 |
| Part A: Monotherapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 42 | 65.88 Units on a scale | Standard Deviation 12.01 |
| Part A: Monotherapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 70 | 59.57 Units on a scale | Standard Deviation 7.14 |
| Part A: Monotherapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 28 | 65.44 Units on a scale | Standard Deviation 7.3 |
| Part B: Add-on Therapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 42 | 68.3 Units on a scale | Standard Deviation 12.7 |
| Part B: Add-on Therapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 28 | 67.0 Units on a scale | Standard Deviation 10.9 |
| Part B: Add-on Therapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Baseline | 71.4 Units on a scale | Standard Deviation 10.3 |
| Part B: Add-on Therapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 84 (Week 12) | 64.4 Units on a scale | Standard Deviation 12.2 |
| Part B: Add-on Therapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 56 | 64.3 Units on a scale | Standard Deviation 11.7 |
| Part B: Add-on Therapy (Placebo) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 14 | 67.3 Units on a scale | Standard Deviation 8.5 |
| Part B: Add-on Therapy (45 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 42 | 73.3 Units on a scale | Standard Deviation 9.8 |
| Part B: Add-on Therapy (45 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Baseline | 62.8 Units on a scale | Standard Deviation 6.7 |
| Part B: Add-on Therapy (45 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 14 | 69.5 Units on a scale | Standard Deviation 13.5 |
| Part B: Add-on Therapy (45 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 28 | 81.3 Units on a scale | Standard Deviation 4.7 |
| Part B: Add-on Therapy (45 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 56 | 70.0 Units on a scale | Standard Deviation 7.1 |
| Part B: Add-on Therapy (45 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 84 (Week 12) | 74.8 Units on a scale | Standard Deviation 7.2 |
| Part B: Add-on Therapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 42 | 61.8 Units on a scale | Standard Deviation 10.9 |
| Part B: Add-on Therapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 84 (Week 12) | 59.0 Units on a scale | Standard Deviation 11.1 |
| Part B: Add-on Therapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 56 | 63.2 Units on a scale | Standard Deviation 14.4 |
| Part B: Add-on Therapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 28 | 66.8 Units on a scale | Standard Deviation 11.4 |
| Part B: Add-on Therapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 14 | 67.4 Units on a scale | Standard Deviation 10.5 |
| Part B: Add-on Therapy (150 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Baseline | 69.6 Units on a scale | Standard Deviation 11.1 |
| Part B: Add-on Therapy (300 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 42 | 64.1 Units on a scale | Standard Deviation 12.5 |
| Part B: Add-on Therapy (300 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Baseline | 67.8 Units on a scale | Standard Deviation 11.1 |
| Part B: Add-on Therapy (300 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 28 | 66.5 Units on a scale | Standard Deviation 11.1 |
| Part B: Add-on Therapy (300 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 56 | 61.4 Units on a scale | Standard Deviation 11.7 |
| Part B: Add-on Therapy (300 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 84 (Week 12) | 60.9 Units on a scale | Standard Deviation 11.3 |
| Part B: Add-on Therapy (300 mg) | Positive and Negative Syndrome Scale (PANSS) Total Scores | Day 14 | 67.9 Units on a scale | Standard Deviation 13.6 |