Schizophrenia
Conditions
Brief summary
The purpose of the study is to evaluate the efficacy, safety, and tolerability of different dose regimens of TV-46000 administered subcutaneously (SC) as compared to placebo during maintenance treatment in adult and adolescent participants with schizophrenia. The study will include male and female participants, 13 to 65 years of age, who have a confirmed diagnosis of schizophrenia, are clinically stable, and are eligible for risperidone treatment
Interventions
DRUGTV-46000
TV-46000 will be administered per dose and schedule specified in the arm.
DRUGPlacebo
Placebo matching to TV-46000 will be administered per schedule specified in the arm.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The participant has a diagnosis of schizophrenia for \>1 year and has had ≥1 episode of relapse in the last 24 months. * The participant has been responsive to an antipsychotic treatment (other than clozapine) in the past year based on discussions with family members or healthcare professionals. * The participant has a stable place of residence for the previous 3 months before screening, and changes in residence are not anticipated over the course of study participation. * The participant has no significant life events that could affect study outcomes expected throughout the period of study participation. * Women of childbearing potential and sexually-active female adolescents must agree not to try to become pregnant, and, unless they have exclusively same-sex partners, must agree to use a highly effective method of contraception, and agree to continue use of this method beginning 1 month before the first administration of study drugs and for the duration of the study and for 120 days after the last injection of study drug. * The participant, if adult or adolescent male, is surgically sterile, or, if capable of producing offspring, or has exclusively same-sex partners or is currently using an approved method of birth control and agrees to the continued use of this method for the duration of the study (and for 120 days after the last dose of study drug). Male participants with sex partners who are women of childbearing potential must use condoms even if surgically sterile * Additional criteria apply, please contact the investigator for more information
Exclusion criteria
* The participant has a current clinically significant Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, or amnestic or other cognitive disorders, or borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder. * The participant is currently on clozapine or received electroconvulsive therapy in the last 12 months. * The participant has a history of epilepsy or seizures, neuroleptic malignant syndrome, tardive dyskinesia, or other medical condition that would expose the participant to undue risk. * The participant has a positive serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B surface antigen, and/or hepatitis C. * The participant has current or history of known hypersensitivity to risperidone or any of the excipients of TV-46000 or the oral formulation of risperidone used in the stabilization phase. * The participant has a substance use disorder, including alcohol and benzodiazepines but excluding nicotine and caffeine. * The participant has previously participated in a Teva-sponsored clinical study with TV-46000. * The participant is a pregnant or lactating female. * The participant has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery). * The participant has used an investigational drug within 3 months prior to screening or has participated in a non-drug clinical trial within 30 days prior to screening. * Additional criteria apply, please contact the investigator for more information
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set | From randomization up to 108 weeks | Relapse was defined as 1 or more of the following items: • Clinical Global Impression-Improvement (CGI-I) of ≥5, and - an increase of any of the 4 Positive and Negative Syndrome Scale (PANSS) items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • Clinical Global Impression-Severity of Suicidality (CGI-SS) of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (number of participants with impending relapse). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Impending Relapse | Week 24 | Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Impending relapse rate at Week 24 was estimated using the Kaplan-Meier product estimate. |
| Number of Participants Who Maintain Stability at the Endpoint | At the endpoint (up to 108 weeks) | Stability is defined as meeting all of the following criteria for at least 4 consecutive weeks: outpatient status; PANSS total score ≤80; minimal presence of specific psychotic symptoms on the PANSS, as measured by a score of ≤4 on each of the following items: conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content; Clinical Global Impression of Severity (CGI-S) score ≤4 (moderately ill); and CGI-SS score ≤2 (mildly suicidal) on Part 1 and ≤5 (minimally worsened) on Part 2. The last valid participant assessment was used as the endpoint. |
| Number of Participants Achieving Remission at the Endpoint | At Endpoint (up to 108 weeks) | The remission was achieved for participants who did not relapse during the study and for over a period of at least 6 months preceding the endpoint, maintained scores of = 3 on each of the 8 specific PANSS items: P1 (delusions), G9 (unusual thought content), P3 (hallucinatory behavior), P2 (conceptual disorganization), G5 (mannerisms/posturing), N1 (blunted affect), N4 (social withdrawal), and N6 (lack of spontaneity). The last valid participant assessment was used as the endpoint. |
| Observed Rate of Impending Relapse (Number of Participants With Impending Relapse) at the Endpoint | At the Endpoint (up to 108 weeks) | Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Observed rate of impending relapse was calculated as the number of participants who relapsed by endpoint divided by the number of participants in each treatment group, using the last valid participant assessment as the endpoint. |
| Time to Impending Relapse (Number of Participants With Impending Relapse) in the Adolescent Participants | From randomization up to 108 weeks | Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (adolescents) (number of participants with impending relapse). |
| Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Baseline, endpoint and end of treatment (up to Week 108) | The DAI-10 is a 10-item questionnaire to assess 1) subjective experience of drug and 2) attitudes and beliefs toward neuroleptics which may influence compliance in schizophrenia participants. The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a participant who was fully adherent to the prescribed medication answered as True and 4 items (2, 5, 6, and 8) that a participant who was fully adherent to the prescribed medication answered as False. A correct answer was scored +1 and an incorrect answer was scored -1. The total score was the sum of pluses and minuses, which ranged from -10 to 10 in increments of 2. A positive total score indicated a positive subjective response (compliant) and a negative total score indicated a negative subjective response (non-compliance). Higher scores denoted better compliance. The last valid participant assessment was used as the endpoint. |
| Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Baseline, endpoint and end of treatment (up to Week 108) | The SQLS comprises 33 items categorized in 2 domains: psychosocial feelings (20 items) and cognition and vitality (13 items). The items were scored on a 5-point scale (1 - never, 2 - rarely, 3 - sometimes, 4 - often, 5 - always). Individual domain and total scores were standardized by scoring algorithm to a 0 (best health status) to 100 (worst health status) scale, with higher scores indicating comparatively lower quality of life. The last valid participant assessment was used as the endpoint. |
| Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set | From randomization up to 108 weeks | Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (adults and adolescents) (number of participants with impending relapse). |
| Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment | Baseline, end of treatment (up to 108 weeks) | The AIMS is a 14-item scale that includes assessments of orofacial movements, extremity and truncal dyskinesia, examiner's judgment of global severity, subjective measures of awareness of movements and distress, and a yes/no assessment of problems concerning teeth and/or dentures. Total AIMS score is a sum of item 1 through 7. Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 0 (no dyskinesia) to 4 (severe dyskinesia) scale. Total AIMS score for Items 1-7 ranged from 0 to 28; with higher scores indicating greater severity of the condition. |
| Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment | Baseline, end of treatment (up to 108 weeks) | The SAS is a 10-item instrument for the assessment of neuroleptic-induced parkinsonism. The items on the scale include measurements of hypokinesia, rigidity, glabellar reflex, tremor, and salivation. Each item was rated on a 5-point scale (0 \[None/Normal\] to 4 \[Extreme/Severe\]). The mean score was calculated by adding the individual item scores and dividing by 10. The total mean score ranged from 0-4, with a higher score indicating greater severity of symptoms. |
| Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment | Baseline, end of treatment (up to 108 weeks) | The BARS is an instrument that assesses the severity of drug-induced akathisia. The BARS includes 3 items for rating objective restless movements, subjective restlessness, and any subjective distress associated with akathisia that were scored on a 4-point scale of 0 (normal/no distress) to 3 (constant restlessness/severe distress). Total score was the sum of scores of each item and ranged from 0-9, with higher scores indicating greater severity of akathisia. |
| Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Baseline, post-baseline (up to 108 weeks) | The C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior was defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. |
| Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment | Baseline, end of treatment (up to 108 weeks) | The CDSS is specifically designed to assess the level of depression separate from the positive, negative, and EPS in schizophrenia. This clinician-administered instrument consists of 9 items, each rated on a 4-point scale from 0 (absent) to 3 (severe) that were added together to form the total CDSS depression score of the participant. The total score ranged from 0-27, with higher scores indicating greater severity of the condition. |
| Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment | Baseline, end of treatment (up to 108 weeks) | The CGI-SS scale provides an overall clinician-rated assessment of the risk of suicidality. The CGI-SS consists of a 5-point scale in Part 1 (the most severe level of suicidality experience) ranging from 1 (not at all suicidal) to 5 (attempted suicide) and a 7-point scale in Part 2 (change in participant suicidality) ranging from 1 (very much improved) to 7 (very much worse). |
| Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | 1 hour prior to dosing at Baseline (Day 1) and at the end of treatment visit (up to 108 weeks) | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From randomization up to 120 days after last dose of study drug (up to Week 125) | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
Countries
Bulgaria, United States
Participant flow
Pre-assignment details
Participants were randomized to receive TV-46000 once monthly (q1m) subcutaneous (SC) injections, TV-46000 once every 2 months (q2m) SC injections, or placebo q1m SC injections in a 1:1:1 ratio. Open-label oral risperidone (2 to 5 mg/day) was used to stabilize participants to the treatments (the dose was based on clinical judgment) before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received an SC injection of placebo matched to TV-46000 at baseline and q4w thereafter. Participants continued treatment until they experienced a relapse event; met 1 or more of the study discontinuation or withdrawal criteria; or remained relapse-free during the double-blind phase until the study was terminated. | 181 |
| TV-46000 q1m Participants received an SC injection of TV-46000 at baseline and q4w thereafter. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. Participants continued treatment until they experienced a relapse event; met 1 or more of the study discontinuation or withdrawal criteria; or remained relapse-free during the double-blind phase until the study was terminated. | 183 |
| TV-46000 q2m Participants received an SC injection of TV-46000 at baseline and q8w thereafter, and a placebo SC injection 4 weeks after baseline and q8w thereafter. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. Participants continued treatment until they experienced a relapse event; met 1 or more of the study discontinuation or withdrawal criteria; or remained relapse-free during the double-blind phase until the study was terminated. | 180 |
| Total | 544 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 | 2 |
| Overall Study | Death | 1 | 0 | 4 |
| Overall Study | Lost to Follow-up | 17 | 15 | 12 |
| Overall Study | Other than specified | 1 | 3 | 3 |
| Overall Study | Protocol Violation | 5 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 12 | 17 | 16 |
Baseline characteristics
| Characteristic | Total | TV-46000 q2m | TV-46000 q1m | Placebo |
|---|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 10.98 | 48.1 years STANDARD_DEVIATION 11.09 | 50.6 years STANDARD_DEVIATION 10.3 | 49.2 years STANDARD_DEVIATION 11.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 117 Participants | 36 Participants | 39 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 427 Participants | 144 Participants | 144 Participants | 139 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 7 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black or African American | 322 Participants | 110 Participants | 108 Participants | 104 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not Reported | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other | 4 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 206 Participants | 66 Participants | 72 Participants | 68 Participants |
| Sex: Female, Male Female | 212 Participants | 70 Participants | 71 Participants | 71 Participants |
| Sex: Female, Male Male | 332 Participants | 110 Participants | 112 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 179 | 0 / 183 | 4 / 180 |
| other Total, other adverse events | 35 / 179 | 49 / 183 | 48 / 180 |
| serious Total, serious adverse events | 14 / 179 | 8 / 183 | 10 / 180 |
Outcome results
Primary
Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set
Relapse was defined as 1 or more of the following items: • Clinical Global Impression-Improvement (CGI-I) of ≥5, and - an increase of any of the 4 Positive and Negative Syndrome Scale (PANSS) items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • Clinical Global Impression-Severity of Suicidality (CGI-SS) of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (number of participants with impending relapse).
Time frame: From randomization up to 108 weeks
Population: Intent-to-treat (ITT) analysis set included adult participants randomized to the double-blind maintenance treatment, regardless if they had received treatment or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set | 53 Participants |
| TV-46000 q1m | Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set | 13 Participants |
| TV-46000 q2m | Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set | 23 Participants |
Comparison: Analysis was performed using the stratified Cox proportional hazard model, with treatment (placebo, TV-46000 q1m and TV-46000 q2m or placebo and TV-46000 overall \[including q1m and q2m\]) as explanatory variable and sex-dose as a stratification factor, and the stratified log rank test p-value (sex-dose as a stratification factor) referred to (TV-46000/placebo) comparison.p-value: <0.000195% CI: [0.109, 0.367]Log Rank
Comparison: Analysis was performed using the stratified Cox proportional hazard model, with treatment (placebo, TV-46000 q1m and TV-46000 q2m or placebo and TV-46000 overall \[including q1m and q2m\]) as explanatory variable and sex-dose as a stratification factor, and the stratified log rank test p-value (sex-dose as a stratification factor) referred to (TV-46000/placebo) comparison.p-value: <0.000195% CI: [0.227, 0.618]Log Rank
Secondary
Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment
The CDSS is specifically designed to assess the level of depression separate from the positive, negative, and EPS in schizophrenia. This clinician-administered instrument consists of 9 items, each rated on a 4-point scale from 0 (absent) to 3 (severe) that were added together to form the total CDSS depression score of the participant. The total score ranged from 0-27, with higher scores indicating greater severity of the condition.
Time frame: Baseline, end of treatment (up to 108 weeks)
Population: Safety analysis set included all randomized participants who received ≥1 dose of study treatment or placebo. Here, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment | Baseline | 1.6 units on a scale | Standard Deviation 2.14 |
| Placebo | Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment | Change at the End of Treatment | -0.4 units on a scale | Standard Deviation 2.72 |
| TV-46000 q1m | Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment | Baseline | 1.3 units on a scale | Standard Deviation 1.92 |
| TV-46000 q1m | Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment | Change at the End of Treatment | -0.3 units on a scale | Standard Deviation 1.39 |
| TV-46000 q2m | Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment | Baseline | 1.5 units on a scale | Standard Deviation 1.93 |
| TV-46000 q2m | Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment | Change at the End of Treatment | -0.8 units on a scale | Standard Deviation 2.24 |
Secondary
Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment
The CGI-SS scale provides an overall clinician-rated assessment of the risk of suicidality. The CGI-SS consists of a 5-point scale in Part 1 (the most severe level of suicidality experience) ranging from 1 (not at all suicidal) to 5 (attempted suicide) and a 7-point scale in Part 2 (change in participant suicidality) ranging from 1 (very much improved) to 7 (very much worse).
Time frame: Baseline, end of treatment (up to 108 weeks)
Population: Safety analysis set included all randomized participants who received ≥1 dose of study treatment or placebo. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment | The most severe level of suicidality experience at Baseline | 1.0 units on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment | Change in participant suicidality at the End of Treatment | 4.0 units on a scale | Standard Deviation 0 |
| TV-46000 q1m | Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment | The most severe level of suicidality experience at Baseline | 1.0 units on a scale | Standard Deviation 0 |
| TV-46000 q1m | Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment | Change in participant suicidality at the End of Treatment | 4.0 units on a scale | Standard Deviation 0 |
| TV-46000 q2m | Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment | The most severe level of suicidality experience at Baseline | 1.0 units on a scale | Standard Deviation 0 |
| TV-46000 q2m | Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment | Change in participant suicidality at the End of Treatment | 4.0 units on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment
The DAI-10 is a 10-item questionnaire to assess 1) subjective experience of drug and 2) attitudes and beliefs toward neuroleptics which may influence compliance in schizophrenia participants. The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a participant who was fully adherent to the prescribed medication answered as True and 4 items (2, 5, 6, and 8) that a participant who was fully adherent to the prescribed medication answered as False. A correct answer was scored +1 and an incorrect answer was scored -1. The total score was the sum of pluses and minuses, which ranged from -10 to 10 in increments of 2. A positive total score indicated a positive subjective response (compliant) and a negative total score indicated a negative subjective response (non-compliance). Higher scores denoted better compliance. The last valid participant assessment was used as the endpoint.
Time frame: Baseline, endpoint and end of treatment (up to Week 108)
Population: ITT analysis set included adult participants randomized to the double-blind maintenance treatment, regardless if they had received treatment or not. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Change at the Endpoint | -0.8 units on a scale | Standard Deviation 3.88 |
| Placebo | Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Baseline | 6.1 units on a scale | Standard Deviation 3.23 |
| Placebo | Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Change at the End of Treatment | -0.9 units on a scale | Standard Deviation 3.42 |
| TV-46000 q1m | Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Change at the Endpoint | 0.1 units on a scale | Standard Deviation 3.34 |
| TV-46000 q1m | Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Baseline | 5.8 units on a scale | Standard Deviation 3.63 |
| TV-46000 q1m | Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Change at the End of Treatment | 0.3 units on a scale | Standard Deviation 2.84 |
| TV-46000 q2m | Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Baseline | 5.7 units on a scale | Standard Deviation 3.13 |
| TV-46000 q2m | Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Change at the End of Treatment | 0.3 units on a scale | Standard Deviation 3.51 |
| TV-46000 q2m | Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment | Change at the Endpoint | -0.3 units on a scale | Standard Deviation 3.65 |
Secondary
Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment
The SQLS comprises 33 items categorized in 2 domains: psychosocial feelings (20 items) and cognition and vitality (13 items). The items were scored on a 5-point scale (1 - never, 2 - rarely, 3 - sometimes, 4 - often, 5 - always). Individual domain and total scores were standardized by scoring algorithm to a 0 (best health status) to 100 (worst health status) scale, with higher scores indicating comparatively lower quality of life. The last valid participant assessment was used as the endpoint.
Time frame: Baseline, endpoint and end of treatment (up to Week 108)
Population: ITT analysis set included adult participants randomized to the double-blind maintenance treatment, regardless if they had received treatment or not. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Change at the Endpoint | 0.9 units on a scale | Standard Deviation 14.24 |
| Placebo | Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Baseline | 34.0 units on a scale | Standard Deviation 16.06 |
| Placebo | Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Change at the End of Treatment | -2.3 units on a scale | Standard Deviation 13.26 |
| TV-46000 q1m | Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Change at the Endpoint | -4.5 units on a scale | Standard Deviation 14.31 |
| TV-46000 q1m | Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Baseline | 33.1 units on a scale | Standard Deviation 16.79 |
| TV-46000 q1m | Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Change at the End of Treatment | -7.2 units on a scale | Standard Deviation 13.79 |
| TV-46000 q2m | Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Baseline | 34.2 units on a scale | Standard Deviation 15.7 |
| TV-46000 q2m | Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Change at the End of Treatment | -7.3 units on a scale | Standard Deviation 12.3 |
| TV-46000 q2m | Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment | Change at the Endpoint | -4.1 units on a scale | Standard Deviation 15.23 |
Secondary
Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment
The SAS is a 10-item instrument for the assessment of neuroleptic-induced parkinsonism. The items on the scale include measurements of hypokinesia, rigidity, glabellar reflex, tremor, and salivation. Each item was rated on a 5-point scale (0 \[None/Normal\] to 4 \[Extreme/Severe\]). The mean score was calculated by adding the individual item scores and dividing by 10. The total mean score ranged from 0-4, with a higher score indicating greater severity of symptoms.
Time frame: Baseline, end of treatment (up to 108 weeks)
Population: Safety analysis set included all randomized participants who received ≥1 dose of study treatment or placebo. Here, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment | Change at the End of Treatment | 0.04 units on a scale | Standard Deviation 0.134 |
| Placebo | Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment | Baseline | 0.07 units on a scale | Standard Deviation 0.137 |
| TV-46000 q1m | Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment | Change at the End of Treatment | 0.02 units on a scale | Standard Deviation 0.211 |
| TV-46000 q1m | Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment | Baseline | 0.09 units on a scale | Standard Deviation 0.195 |
| TV-46000 q2m | Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment | Change at the End of Treatment | 0.00 units on a scale | Standard Deviation 0.102 |
| TV-46000 q2m | Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment | Baseline | 0.06 units on a scale | Standard Deviation 0.134 |
Secondary
Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment
The AIMS is a 14-item scale that includes assessments of orofacial movements, extremity and truncal dyskinesia, examiner's judgment of global severity, subjective measures of awareness of movements and distress, and a yes/no assessment of problems concerning teeth and/or dentures. Total AIMS score is a sum of item 1 through 7. Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 0 (no dyskinesia) to 4 (severe dyskinesia) scale. Total AIMS score for Items 1-7 ranged from 0 to 28; with higher scores indicating greater severity of the condition.
Time frame: Baseline, end of treatment (up to 108 weeks)
Population: Safety analysis set included all randomized participants who received ≥1 dose of study treatment or placebo. Here, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment | Baseline | 0.4 units on a scale | Standard Deviation 1.3 |
| Placebo | Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment | Change at the End of Treatment | 0.0 units on a scale | Standard Deviation 1.1 |
| TV-46000 q1m | Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment | Baseline | 0.5 units on a scale | Standard Deviation 1.83 |
| TV-46000 q1m | Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment | Change at the End of Treatment | 0.1 units on a scale | Standard Deviation 0.62 |
| TV-46000 q2m | Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment | Baseline | 0.2 units on a scale | Standard Deviation 0.79 |
| TV-46000 q2m | Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment | Change at the End of Treatment | 0.1 units on a scale | Standard Deviation 1 |
Secondary
Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment
The BARS is an instrument that assesses the severity of drug-induced akathisia. The BARS includes 3 items for rating objective restless movements, subjective restlessness, and any subjective distress associated with akathisia that were scored on a 4-point scale of 0 (normal/no distress) to 3 (constant restlessness/severe distress). Total score was the sum of scores of each item and ranged from 0-9, with higher scores indicating greater severity of akathisia.
Time frame: Baseline, end of treatment (up to 108 weeks)
Population: Safety analysis set included all randomized participants who received ≥1 dose of study treatment or placebo. Here, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment | Baseline | 0.2 units on a scale | Standard Deviation 0.63 |
| Placebo | Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment | Change at the End of Treatment | -0.1 units on a scale | Standard Deviation 0.56 |
| TV-46000 q1m | Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment | Baseline | 0.1 units on a scale | Standard Deviation 0.39 |
| TV-46000 q1m | Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment | Change at the End of Treatment | 0.0 units on a scale | Standard Deviation 0.51 |
| TV-46000 q2m | Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment | Baseline | 0.2 units on a scale | Standard Deviation 0.57 |
| TV-46000 q2m | Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment | Change at the End of Treatment | -0.1 units on a scale | Standard Deviation 0.56 |
Secondary
Number of Participants Achieving Remission at the Endpoint
The remission was achieved for participants who did not relapse during the study and for over a period of at least 6 months preceding the endpoint, maintained scores of = 3 on each of the 8 specific PANSS items: P1 (delusions), G9 (unusual thought content), P3 (hallucinatory behavior), P2 (conceptual disorganization), G5 (mannerisms/posturing), N1 (blunted affect), N4 (social withdrawal), and N6 (lack of spontaneity). The last valid participant assessment was used as the endpoint.
Time frame: At Endpoint (up to 108 weeks)
Population: ITT analysis set included adult participants randomized to the double-blind maintenance treatment, regardless if they had received treatment or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving Remission at the Endpoint | 30 Participants |
| TV-46000 q1m | Number of Participants Achieving Remission at the Endpoint | 39 Participants |
| TV-46000 q2m | Number of Participants Achieving Remission at the Endpoint | 42 Participants |
Secondary
Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline
The C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior was defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.
Time frame: Baseline, post-baseline (up to 108 weeks)
Population: Safety analysis set included all randomized participants who received ≥1 dose of study treatment or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Baseline: Suicidal behavior | 0 Participants |
| Placebo | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Baseline: Suicidal ideation | 6 Participants |
| Placebo | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Post-baseline: Suicidal behavior | 3 Participants |
| Placebo | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Post-baseline: Suicidal ideation | 12 Participants |
| TV-46000 q1m | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Post-baseline: Suicidal ideation | 7 Participants |
| TV-46000 q1m | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Baseline: Suicidal behavior | 0 Participants |
| TV-46000 q1m | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Post-baseline: Suicidal behavior | 1 Participants |
| TV-46000 q1m | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Baseline: Suicidal ideation | 5 Participants |
| TV-46000 q2m | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Post-baseline: Suicidal ideation | 12 Participants |
| TV-46000 q2m | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Baseline: Suicidal ideation | 7 Participants |
| TV-46000 q2m | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Post-baseline: Suicidal behavior | 1 Participants |
| TV-46000 q2m | Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline | Baseline: Suicidal behavior | 3 Participants |
Secondary
Number of Participants Who Maintain Stability at the Endpoint
Stability is defined as meeting all of the following criteria for at least 4 consecutive weeks: outpatient status; PANSS total score ≤80; minimal presence of specific psychotic symptoms on the PANSS, as measured by a score of ≤4 on each of the following items: conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content; Clinical Global Impression of Severity (CGI-S) score ≤4 (moderately ill); and CGI-SS score ≤2 (mildly suicidal) on Part 1 and ≤5 (minimally worsened) on Part 2. The last valid participant assessment was used as the endpoint.
Time frame: At the endpoint (up to 108 weeks)
Population: ITT analysis set included adult participants randomized to the double-blind maintenance treatment, regardless if they had received treatment or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Maintain Stability at the Endpoint | 110 Participants |
| TV-46000 q1m | Number of Participants Who Maintain Stability at the Endpoint | 159 Participants |
| TV-46000 q2m | Number of Participants Who Maintain Stability at the Endpoint | 143 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: From randomization up to 120 days after last dose of study drug (up to Week 125)
Population: Safety analysis set included all randomized participants who received ≥1 dose of study treatment or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 92 Participants |
| TV-46000 q1m | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 111 Participants |
| TV-46000 q2m | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 121 Participants |
Secondary
Observed Rate of Impending Relapse (Number of Participants With Impending Relapse) at the Endpoint
Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Observed rate of impending relapse was calculated as the number of participants who relapsed by endpoint divided by the number of participants in each treatment group, using the last valid participant assessment as the endpoint.
Time frame: At the Endpoint (up to 108 weeks)
Population: ITT analysis set included adult participants randomized to the double-blind maintenance treatment, regardless if they had received treatment or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Observed Rate of Impending Relapse (Number of Participants With Impending Relapse) at the Endpoint | 53 Participants |
| TV-46000 q1m | Observed Rate of Impending Relapse (Number of Participants With Impending Relapse) at the Endpoint | 13 Participants |
| TV-46000 q2m | Observed Rate of Impending Relapse (Number of Participants With Impending Relapse) at the Endpoint | 23 Participants |
Secondary
Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone)
Time frame: 1 hour prior to dosing at Baseline (Day 1) and at the end of treatment visit (up to 108 weeks)
Population: Pharmacokinetics (PK) analysis set included all randomized participants who received ≥1 dose of study treatment or placebo and who also had ≥1 plasma concentration measured. Here, 'Number analyzed' signifies participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Risperidone at Baseline | 4.694 ng/mL |
| Placebo | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Risperidone at the End of Treatment | 1.323 ng/mL |
| Placebo | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | 9-OH-Risperidone at Baseline | 14.965 ng/mL |
| Placebo | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | 9-OH-Risperidone at the End of Treatment | 2.982 ng/mL |
| Placebo | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Total Active Moiety at Baseline | 19.060 ng/mL |
| Placebo | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Total Active Moiety at the End of Treatment | 4.078 ng/mL |
| TV-46000 q1m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Total Active Moiety at the End of Treatment | 38.429 ng/mL |
| TV-46000 q1m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Risperidone at Baseline | 6.452 ng/mL |
| TV-46000 q1m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | 9-OH-Risperidone at the End of Treatment | 26.202 ng/mL |
| TV-46000 q1m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Total Active Moiety at Baseline | 24.200 ng/mL |
| TV-46000 q1m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Risperidone at the End of Treatment | 13.215 ng/mL |
| TV-46000 q1m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | 9-OH-Risperidone at Baseline | 18.473 ng/mL |
| TV-46000 q2m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Risperidone at the End of Treatment | 8.838 ng/mL |
| TV-46000 q2m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | 9-OH-Risperidone at Baseline | 15.187 ng/mL |
| TV-46000 q2m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Total Active Moiety at the End of Treatment | 25.947 ng/mL |
| TV-46000 q2m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | 9-OH-Risperidone at the End of Treatment | 17.778 ng/mL |
| TV-46000 q2m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Risperidone at Baseline | 5.364 ng/mL |
| TV-46000 q2m | Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) | Total Active Moiety at Baseline | 19.945 ng/mL |
Secondary
Proportion of Participants With Impending Relapse
Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Impending relapse rate at Week 24 was estimated using the Kaplan-Meier product estimate.
Time frame: Week 24
Population: ITT analysis set included adult participants randomized to the double-blind maintenance treatment, regardless if they had received treatment or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants With Impending Relapse | 0.28 proportion of participants |
| TV-46000 q1m | Proportion of Participants With Impending Relapse | 0.07 proportion of participants |
| TV-46000 q2m | Proportion of Participants With Impending Relapse | 0.11 proportion of participants |
Secondary
Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set
Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (adults and adolescents) (number of participants with impending relapse).
Time frame: From randomization up to 108 weeks
Population: eITT analysis set included all participants (adults and adolescents) randomized to the double-blind maintenance stage treatment, regardless if they had received treatment or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set | 53 Participants |
| TV-46000 q1m | Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set | 13 Participants |
| TV-46000 q2m | Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set | 24 Participants |
Secondary
Time to Impending Relapse (Number of Participants With Impending Relapse) in the Adolescent Participants
Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (adolescents) (number of participants with impending relapse).
Time frame: From randomization up to 108 weeks
Population: eITT analysis set included all participants (adults and adolescents) randomized to the double-blind maintenance stage treatment, regardless if they had received treatment or not. Here, 'Overall number of participants analyzed' signifies adolescent participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TV-46000 q2m | Time to Impending Relapse (Number of Participants With Impending Relapse) in the Adolescent Participants | 1 Participants |