Schizophrenia
Conditions
Keywords
Schizophrenia, Schizophrenic, Schizophrenias, Risperidone, Long-acting Risperidone, Atrigel, Subcutaneous
Brief summary
This is a Phase 3, open label study administering RBP-7000 in the treatment of patients with schizophrenia. Study will assess the long-term safety and tolerability of RBP-7000 subcutaneous (SC) injections in subjects with schizophrenia and to continue collecting clinical outcome data with RBP-7000 SC injections in subjects with schizophrenia using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Illness (CGI-S) scale.
Detailed description
Patients to be screened must be diagnosed with schizophrenia with a designated score based on the PANSS, as confirmed by a State, Assessability, Face, Ecological and Rule (SAFER) interview. De novo patients are patients who are already receiving 3- or 4-mg oral risperidone/day and will not have to complete the run-in or conversion phases (see below) and will be assigned to receive RBP-7000 after eligibility has been confirmed. Patients who completed the double-blind, placebo-controlled, efficacy study of RBP-7000 (RB-US-09-0010, NCT02109562), conducted in patients with acute schizophrenia (referred to as roll-over patients) will be screened. All patients will be assigned the 120 mg dose of RBP-7000, which is subject to a one-time down-titration to 90-mg RBP-7000 for tolerability, at the investigator's discretion. Patients receiving the 90-mg dose of RBP-7000 who exhibit a worsening in psychiatric symptoms, confirmed by a total PANSS score \>70 or a 20% increase in the PANSS score from the previous assessment at the 120-mg dose level (before the dose was decreased to 90 mg), can receive a one-time, up-titration back to 120-mg RBP-7000 at the discretion of the investigator. De novo patients entering into the study are those patients who did not participate in study RB-US-09-0010 (NCT02109562) and are allocated into three groups with different pre-study procedures to prepare for the treatment period: * Run-in patients are patients who are not already receiving oral risperidone (as no other antipsychotic medications are allowed during study participation) and will begin a 14-day run-in period by titrating up to a dose of 3 or 4 mg oral risperidone/day before the first injection of RBP-7000. * Conversion patients are patients who are receiving oral risperidone doses other than 3 or 4mg/day and will begin a 7-day conversion period to achieve an oral risperidone dose level of 3 or 4-mg before the first injection of RBP-7000, only if clinically indicated. * De novo patients taking an oral risperidone dose of 3 or 4 mg/day prestudy will (once screened/enrolled) receive the first injection of RBP-7000. Roll-over patients entering into the study are patients who completed 56 days of double-blind treatment in Study RB-US-09-0010. These patients will be eligible to enter the current study provided that continuation of treatment is clinically warranted, as judged by the investigator, and that there have been no significant protocol deviations or clinically relevant adverse events (AEs) that would preclude inclusion in this study. Roll-over patients will not undergo the complete screening process and will not require either a run-in or conversion period with oral risperidone. On Day 1 of the open-label study (which is Day 57 of Study RB-US-09-0010), patients will receive their first injection (120 mg) of open label RBP-7000.
Interventions
DRUGRBP-7000
120-mg RBP-7000 dose delivered by subcutaneous injection every 28 days for a total of 13 injections (for roll-over participants, the first two injections took place under study RB-US-09-0010). A one-time down-titration to 90 mg RBP-7000 is permitted at the investigator's discretion should the participant have tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator. RBP-7000 is a combination of the ATRIGEL Delivery System and risperidone. The ATRIGEL Delivery System allows for sustained-release of risperidone in a controlled manner.
Sponsors
Indivior Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
De Novo Patients * Diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual, Edition 4, text revision (DSM-IV-TR) criteria * Total PANSS score \<=70 at the time of screening (Visit 1) * Otherwise healthy on the basis of physical examinatIon * Provided written informed consent Roll-over Patients * Provided written consent to participate in this study * Be considered eligible to enroll based on End of Study (EOS) (Day 57 of Study RB-US-09-0010) assessments and the medical judgment of the investigator
Exclusion criteria
De Novo Patients * Patients taking daily oral risperidone at a dose plus/minus 6 mg/day * Patients taking any risperidone or 9-hydroxyrisperidone long-acting injectable formulation within 120 days of study screening (Visit 1) * Patients who have received a long-acting injectable antipsychotic within 120 days of screening (Visit 1) * Patients with evidence or history (in the past six months prior to screening) of a significant hepatic disorder that may either compromise patient safety or interfere with the safety and/or outcome evaluation of the study drug, including: * Acute or chronic hepatitis, including but not limited to hepatitis B or C * Total bilirubin greater than 1.5 times the upper limit of normal (ULN), or * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 times ULN * Patients with a history of drug-induced leukopenia * Patients with other medical conditions including, but not limited to, history of heart attack (myocardial infarction) or brain injury (traumatic injury with loss of consciousness and/or cerebrovascular accident), and clinically significant low blood pressure or arrhythmias as interpreted by the primary investigator (PI) or medically qualified sub-investigator * Patients with epilepsy or other seizure disorders, Parkinson's disease or dementia Roll-over Patients * Patients requiring an inpatient treatment setting at the end of Study RB-US-09-0010 * Patients with an unstable medical condition developed during Study RB-US-09-0010 * Women of childbearing potential who have a positive pregnancy test at screening (Visit 1), who are pregnant or breastfeeding, seeking pregnancy, or failing to use adequate contraceptive methods during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Treatment-Emergent Adverse Events (TEAE) | Day 1 up to week 52 | An adverse event (AE) is defined as any study-related event that represents a change (positive or negative) in frequency or severity from a baseline (prestudy) event (if any), regardless of the presence of causal relationship or medical significance. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the first study dose date. AEs are determined by the Investigator to be related or not related to the study drug. A serious AE (SAE) is defined by federal regulation as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Although a subject may have had 2 or more adverse experiences the subject is counted only once in a category. The same subject may appear in different categories. |
| Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Day 1 up to week 52 | An adverse event (AE) is defined as any study-related event that represents a change (positive or negative) in frequency or severity from a baseline (prestudy) event (if any), regardless of the presence of causal relationship or medical significance. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the first study dose date. Adverse events were coded using MedDRA version 17.0. Preferred terms linked to injection site AEs are reported. Although a participant may have had 2 or more AEs, the subject is counted only once in each preferred term category. The same subject may appear in different preferred term categories. |
| Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline | Baseline (Day 0), Treatment (Day 1 up to Week 52) | Participants who were found to have gain \>=7% and \>=10% of their baseline weight at any point during the study (including unscheduled assessments) once treatment began. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52) | The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor judgement, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicate improvements in symptoms. |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | Baseline (Day 0), End of Study (approximately Week 52) | PANSS subscales: * Positive scale assesses 7 items: delusions, conceptual disorganization, hallucinations, excitement, grandiosity, suspiciousness/persecution, and hostility. Scale: 7 (absent) to 49 (extreme psychopathology) * Negative scale assesses 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking. Scale: 7 (absent) to 49 (extreme psychopathology) * General Psychopathology scale assesses 16 items: somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance. Scale: 16 (absent) to 112 (extreme psychopathology) Negative change from baseline scores indicate improvements. |
| Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | Baseline (Day 0), Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52) | The CGI-S rating scale is a 7-point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to Normal, not at all ill and a rating of 7 is equivalent to Among the most extremely ill participants. Negative change from baseline scores indicate improvement in the severity of illness. |
Countries
United States
Participant flow
Pre-assignment details
A total of 820 subjects were screened for study participation at 53 sites in the US. Overall, 500 participants were included in the Safety Population: 92 rollover participants and 408 de novo participants.
Participants by arm
| Arm | Count |
|---|---|
| De Novo Participants Participants who were not part of the previous double-blind study.
Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart.
A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator. | 408 |
| Rollover Placebo Participants who were randomized to the placebo arm in the double-blind study RB-US-09-0010 prior to entering this study.
Treatment consisted of 13 subcutaneous injections of 120 mg RBP-7000 28 days apart.
A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator. | 28 |
| Rollover RBP-7000 90 mg Participants who were randomized to the RBP-7000 90 mg arm in the double-blind study RB-US-09-0010 prior to entering this study.
Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study).
A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator. | 31 |
| Rollover RBP-7000 120 mg Participants who were randomized to the RBP-7000 120 mg arm in the double-blind study RB-US-09-0010 prior to entering this study.
Treatment consisted of 11 subcutaneous injections of 120 mg RBP-7000 28 days apart (13 injections total counting the previous study).
A one-time down-titration to 90 mg RBP-7000 was permitted at the investigator's discretion if the participant had tolerability issues. Participants who received the 90-mg dose of RBP-7000 and exhibited a worsening in psychiatric symptoms could receive a one-time up-titration back to 120 mg RBP-7000 at the discretion of the investigator. | 33 |
| Total | 500 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 46 | 6 | 3 | 2 |
| Overall Study | Lack of Efficacy | 7 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 39 | 3 | 2 | 1 |
| Overall Study | Other | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 27 | 0 | 2 | 3 |
| Overall Study | Protocol Violation | 7 | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 83 | 10 | 8 | 11 |
Baseline characteristics
| Characteristic | Rollover RBP-7000 120 mg | Total | De Novo Participants | Rollover Placebo | Rollover RBP-7000 90 mg |
|---|---|---|---|---|---|
| Age, Continuous | 42.3 years STANDARD_DEVIATION 10.04 | 45.1 years STANDARD_DEVIATION 10.34 | 45.7 years STANDARD_DEVIATION 10.51 | 44.0 years STANDARD_DEVIATION 7.33 | 41.1 years STANDARD_DEVIATION 9.64 |
| Age, Customized 20 years and under | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants |
| Age, Customized 21 to 30 years | 5 Participants | 49 Participants | 39 Participants | 1 Participants | 4 Participants |
| Age, Customized 31 to 40 years | 6 Participants | 106 Participants | 81 Participants | 9 Participants | 10 Participants |
| Age, Customized 41 to 50 years | 12 Participants | 163 Participants | 128 Participants | 12 Participants | 11 Participants |
| Age, Customized 51 to 55 years | 9 Participants | 105 Participants | 85 Participants | 6 Participants | 5 Participants |
| Age, Customized 56 to 65 years | 0 Participants | 74 Participants | 73 Participants | 0 Participants | 1 Participants |
| Body Mass Index | 31.838 kg/m^2 STANDARD_DEVIATION 8.341 | 31.375 kg/m^2 STANDARD_DEVIATION 7.284 | 31.121 kg/m^2 STANDARD_DEVIATION 7.104 | 33.920 kg/m^2 STANDARD_DEVIATION 8.551 | 31.926 kg/m^2 STANDARD_DEVIATION 7.104 |
| Child-bearing Potential No | 8 Participants | 95 Participants | 79 Participants | 5 Participants | 3 Participants |
| Child-bearing Potential Yes | 5 Participants | 66 Participants | 54 Participants | 4 Participants | 3 Participants |
| Clinical Global Impression - Severity Scale (CGI-S) | 3.3 units on a scale STANDARD_DEVIATION 0.89 | 3.4 units on a scale STANDARD_DEVIATION 0.71 | 3.3 units on a scale STANDARD_DEVIATION 0.62 | 3.7 units on a scale STANDARD_DEVIATION 1.09 | 3.8 units on a scale STANDARD_DEVIATION 0.95 |
| Positive and Negative Syndrome Scale (PANSS) | 71.0 units on a scale STANDARD_DEVIATION 13.93 | 60.9 units on a scale STANDARD_DEVIATION 12.04 | 58.0 units on a scale STANDARD_DEVIATION 8.33 | 72.9 units on a scale STANDARD_DEVIATION 20.99 | 76.4 units on a scale STANDARD_DEVIATION 15.99 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 4 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 22 Participants | 354 Participants | 292 Participants | 18 Participants | 22 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 44 Participants | 36 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 31 Participants | 455 Participants | 371 Participants | 24 Participants | 29 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 136 Participants | 109 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Female | 13 Participants | 161 Participants | 133 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Male | 20 Participants | 339 Participants | 275 Participants | 19 Participants | 25 Participants |
| Waist-to-Hip Ratio | 0.935 ratio STANDARD_DEVIATION 0.075 | 0.946 ratio STANDARD_DEVIATION 0.087 | 0.946 ratio STANDARD_DEVIATION 0.09 | 0.936 ratio STANDARD_DEVIATION 0.094 | 0.975 ratio STANDARD_DEVIATION 0.059 |
| Weight | 94.65 kg STANDARD_DEVIATION 23.994 | 93.53 kg STANDARD_DEVIATION 21.463 | 92.80 kg STANDARD_DEVIATION 20.989 | 99.33 kg STANDARD_DEVIATION 25.113 | 96.72 kg STANDARD_DEVIATION 21.305 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 408 | 1 / 28 | 0 / 31 | 0 / 33 |
| other Total, other adverse events | 228 / 408 | 14 / 28 | 17 / 31 | 13 / 33 |
| serious Total, serious adverse events | 25 / 408 | 3 / 28 | 3 / 31 | 3 / 33 |
Outcome results
Primary
Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as any study-related event that represents a change (positive or negative) in frequency or severity from a baseline (prestudy) event (if any), regardless of the presence of causal relationship or medical significance. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the first study dose date. Adverse events were coded using MedDRA version 17.0. Preferred terms linked to injection site AEs are reported. Although a participant may have had 2 or more AEs, the subject is counted only once in each preferred term category. The same subject may appear in different preferred term categories.
Time frame: Day 1 up to week 52
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site erythema | 4 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site pruritus | 21 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site induration | 26 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site nodule | 29 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Influenza like illness | 1 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site irritation | 1 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site discolouration | 1 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Device malfunction | 2 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site swelling | 0 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site reaction | 3 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site bruising | 5 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Implant site nodule | 1 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site discomfort | 2 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Infusion site bruising | 1 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site ulcer | 1 Participants |
| De Novo Participants | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site pain | 52 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site pain | 2 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site discomfort | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Device malfunction | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Implant site nodule | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site nodule | 1 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site induration | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site pruritus | 1 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site erythema | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site bruising | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site reaction | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site discolouration | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Infusion site bruising | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site irritation | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site swelling | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site ulcer | 0 Participants |
| Rollover Placebo | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Influenza like illness | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site erythema | 2 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Device malfunction | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site ulcer | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site bruising | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site reaction | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Implant site nodule | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site discolouration | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Infusion site bruising | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site discomfort | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site pruritus | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site irritation | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site swelling | 1 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site induration | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site pain | 4 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site nodule | 1 Participants |
| Rollover RBP-7000 90 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Influenza like illness | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site induration | 3 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site erythema | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site irritation | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site reaction | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site bruising | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Device malfunction | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site ulcer | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Influenza like illness | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site discomfort | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site nodule | 3 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site pain | 7 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site discolouration | 1 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Implant site nodule | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site swelling | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Infusion site bruising | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs) | Injection site pruritus | 1 Participants |
Primary
Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline
Participants who were found to have gain \>=7% and \>=10% of their baseline weight at any point during the study (including unscheduled assessments) once treatment began.
Time frame: Baseline (Day 0), Treatment (Day 1 up to Week 52)
Population: Safety population of study participants with a baseline weight recorded and at least one post-treatment weight recorded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| De Novo Participants | Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline | >=10% increase from baseline | 67 Participants |
| De Novo Participants | Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline | >=7% increase from baseline | 106 Participants |
| Rollover Placebo | Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline | >=7% increase from baseline | 3 Participants |
| Rollover Placebo | Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline | >=10% increase from baseline | 3 Participants |
| Rollover RBP-7000 90 mg | Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline | >=10% increase from baseline | 2 Participants |
| Rollover RBP-7000 90 mg | Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline | >=7% increase from baseline | 4 Participants |
| Rollover RBP-7000 120 mg | Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline | >=10% increase from baseline | 4 Participants |
| Rollover RBP-7000 120 mg | Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline | >=7% increase from baseline | 5 Participants |
Primary
Participants With Treatment-Emergent Adverse Events (TEAE)
An adverse event (AE) is defined as any study-related event that represents a change (positive or negative) in frequency or severity from a baseline (prestudy) event (if any), regardless of the presence of causal relationship or medical significance. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the first study dose date. AEs are determined by the Investigator to be related or not related to the study drug. A serious AE (SAE) is defined by federal regulation as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Although a subject may have had 2 or more adverse experiences the subject is counted only once in a category. The same subject may appear in different categories.
Time frame: Day 1 up to week 52
Population: Safety population -- participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| De Novo Participants | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 serious TEAE | 25 Participants |
| De Novo Participants | Participants With Treatment-Emergent Adverse Events (TEAE) | 1 or more TEAE | 306 Participants |
| De Novo Participants | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 TEAE related to study drug | 232 Participants |
| De Novo Participants | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to death | 3 Participants |
| De Novo Participants | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 serious and related TEAE | 0 Participants |
| De Novo Participants | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to dose modification | 38 Participants |
| De Novo Participants | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to discontinuation | 47 Participants |
| Rollover Placebo | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 serious and related TEAE | 0 Participants |
| Rollover Placebo | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to discontinuation | 6 Participants |
| Rollover Placebo | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to dose modification | 2 Participants |
| Rollover Placebo | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 serious TEAE | 3 Participants |
| Rollover Placebo | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 TEAE related to study drug | 12 Participants |
| Rollover Placebo | Participants With Treatment-Emergent Adverse Events (TEAE) | 1 or more TEAE | 21 Participants |
| Rollover Placebo | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to death | 1 Participants |
| Rollover RBP-7000 90 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 serious TEAE | 3 Participants |
| Rollover RBP-7000 90 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | 1 or more TEAE | 22 Participants |
| Rollover RBP-7000 90 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 serious and related TEAE | 0 Participants |
| Rollover RBP-7000 90 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to dose modification | 1 Participants |
| Rollover RBP-7000 90 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to discontinuation | 3 Participants |
| Rollover RBP-7000 90 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 TEAE related to study drug | 14 Participants |
| Rollover RBP-7000 90 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to death | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to dose modification | 2 Participants |
| Rollover RBP-7000 120 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 serious and related TEAE | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to discontinuation | 2 Participants |
| Rollover RBP-7000 120 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | 1 or more TEAE | 18 Participants |
| Rollover RBP-7000 120 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 serious TEAE | 3 Participants |
| Rollover RBP-7000 120 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | TEAE leading to death | 0 Participants |
| Rollover RBP-7000 120 mg | Participants With Treatment-Emergent Adverse Events (TEAE) | >=1 TEAE related to study drug | 12 Participants |
Secondary
Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study
The CGI-S rating scale is a 7-point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to Normal, not at all ill and a rating of 7 is equivalent to Among the most extremely ill participants. Negative change from baseline scores indicate improvement in the severity of illness.
Time frame: Baseline (Day 0), Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52)
Population: Safety population. Population counts at each timepoint represent participants with an observation at that timepoint (all participants had baseline assessments).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| De Novo Participants | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | Day 29 | -0.0 units on a scale | Standard Deviation 0.35 |
| De Novo Participants | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | End of Study | -0.2 units on a scale | Standard Deviation 0.66 |
| De Novo Participants | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | Day 169 | -0.1 units on a scale | Standard Deviation 0.48 |
| Rollover Placebo | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | Day 29 | -0.3 units on a scale | Standard Deviation 0.82 |
| Rollover Placebo | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | End of Study | -1.0 units on a scale | Standard Deviation 1.1 |
| Rollover Placebo | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | Day 169 | -0.3 units on a scale | Standard Deviation 1.32 |
| Rollover RBP-7000 90 mg | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | Day 169 | -0.3 units on a scale | Standard Deviation 0.59 |
| Rollover RBP-7000 90 mg | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | Day 29 | -0.2 units on a scale | Standard Deviation 0.8 |
| Rollover RBP-7000 90 mg | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | End of Study | -0.5 units on a scale | Standard Deviation 0.64 |
| Rollover RBP-7000 120 mg | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | Day 29 | -0.1 units on a scale | Standard Deviation 0.71 |
| Rollover RBP-7000 120 mg | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | End of Study | -0.3 units on a scale | Standard Deviation 1.05 |
| Rollover RBP-7000 120 mg | Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study | Day 169 | -0.4 units on a scale | Standard Deviation 0.87 |
Secondary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study
PANSS subscales: * Positive scale assesses 7 items: delusions, conceptual disorganization, hallucinations, excitement, grandiosity, suspiciousness/persecution, and hostility. Scale: 7 (absent) to 49 (extreme psychopathology) * Negative scale assesses 7 items: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking. Scale: 7 (absent) to 49 (extreme psychopathology) * General Psychopathology scale assesses 16 items: somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance. Scale: 16 (absent) to 112 (extreme psychopathology) Negative change from baseline scores indicate improvements.
Time frame: Baseline (Day 0), End of Study (approximately Week 52)
Population: Safety population. Population counts represent participants with an end of study observation (all participants had baseline assessments).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| De Novo Participants | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | Positive subscale | -1.3 units on a scale | Standard Deviation 3.29 |
| De Novo Participants | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | General Psychopathology subscale | -0.4 units on a scale | Standard Deviation 5 |
| De Novo Participants | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | Negative subscale | 1.3 units on a scale | Standard Deviation 3.56 |
| Rollover Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | Negative subscale | -4.0 units on a scale | Standard Deviation 5.93 |
| Rollover Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | General Psychopathology subscale | -8.3 units on a scale | Standard Deviation 6.95 |
| Rollover Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | Positive subscale | -7.8 units on a scale | Standard Deviation 5.49 |
| Rollover RBP-7000 90 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | Negative subscale | -4.1 units on a scale | Standard Deviation 4.6 |
| Rollover RBP-7000 90 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | Positive subscale | -3.7 units on a scale | Standard Deviation 4.08 |
| Rollover RBP-7000 90 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | General Psychopathology subscale | -4.7 units on a scale | Standard Deviation 8.99 |
| Rollover RBP-7000 120 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | Positive subscale | -3.7 units on a scale | Standard Deviation 3.5 |
| Rollover RBP-7000 120 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | General Psychopathology subscale | -6.4 units on a scale | Standard Deviation 7.92 |
| Rollover RBP-7000 120 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study | Negative subscale | -0.9 units on a scale | Standard Deviation 3.78 |
Secondary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study
The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor judgement, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicate improvements in symptoms.
Time frame: Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52)
Population: Safety population. Population counts at each timepoint represent participants with an observation at that timepoint (all participants had baseline assessments).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| De Novo Participants | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | End of Study | -0.4 units on a scale | Standard Deviation 8.67 |
| De Novo Participants | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | Day 169 | -1.2 units on a scale | Standard Deviation 6.84 |
| De Novo Participants | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | Day 29 | -1.2 units on a scale | Standard Deviation 5.7 |
| Rollover Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | Day 169 | -8.2 units on a scale | Standard Deviation 18.96 |
| Rollover Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | End of Study | -20.2 units on a scale | Standard Deviation 15.59 |
| Rollover Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | Day 29 | -4.8 units on a scale | Standard Deviation 11.11 |
| Rollover RBP-7000 90 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | Day 169 | -10.0 units on a scale | Standard Deviation 14.42 |
| Rollover RBP-7000 90 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | Day 29 | -8.3 units on a scale | Standard Deviation 13.43 |
| Rollover RBP-7000 90 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | End of Study | -12.5 units on a scale | Standard Deviation 15.53 |
| Rollover RBP-7000 120 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | End of Study | -10.9 units on a scale | Standard Deviation 13.16 |
| Rollover RBP-7000 120 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | Day 169 | -9.4 units on a scale | Standard Deviation 9.62 |
| Rollover RBP-7000 120 mg | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study | Day 29 | -2.4 units on a scale | Standard Deviation 10.25 |