Schizophrenia
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of TV-44749 in adult participants with schizophrenia. A key secondary objective is to further evaluate the efficacy of TV-44749 based on additional parameters in adult participants with schizophrenia. A secondary objective is to evaluate the safety and tolerability of TV-44749 in adult participants with schizophrenia Another secondary objective of this study is to evaluate the efficacy of TV-44749 from baseline to endpoint in Period 1 in adult participants with schizophrenia. Total study duration is up to 61 weeks, and treatment duration is up to 56 weeks, with weekly visits during the first 8 weeks and then monthly in-clinic visits with weekly calls during the remainder of the treatment period.
Detailed description
Participants with exacerbation of schizophrenia may be included. The study will be composed of 2 periods: Period 1 (the double-blind, placebo-controlled, efficacy and safety period) and Period 2 (open-label long term safety period). For each participant, the duration of Period 1 will be 8 weeks, and the duration of Period 2 will be up to 48 weeks. In Period 1, participants will be randomized to one of 3 TV-44749 treatment groups or a placebo group in a 1:1:1:1 ratio. All participants will be randomized again to one of the TV44749 treatment groups in a 1:1:1 ratio for Period 2. The end-of-treatment and follow-up visits will be at 4 and 8 weeks after the last dose of investigational medicinal product administration, respectively.
Interventions
DRUGTV-44749
In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections
DRUGPlacebo
In Period 1, 2 monthly injections (Period 1 only)
Sponsors
Teva Branded Pharmaceutical Products R&D LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* The participant has a current confirmed diagnosis of schizophrenia according to the DSM-5, for \>1 year * The participant has exacerbation of schizophrenia that started ≤8 weeks prior to screening and would benefit from psychiatric hospitalization or continued hospitalization for symptoms of schizophrenia. * Participants who have received an antipsychotic treatment (other than clozapine) in the past year must have been responsive based on the investigator's judgment (and based on discussions with family members, caregivers, or healthcare professionals, as applicable). * Body mass index between 18.0 and 40.0 kg/m2, inclusive, at the time of screening * Women may be included only if they have a negative beta-human chorionic gonadotropin (β-HCG) test at screening and baseline * Women of childbearing potential 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 prior to the first administration of IMP, and agree to continue the use of this method for the duration of the study, and for 70 days after the last dose of IMP * The participant is in adequate health as determined by medical and psychiatric history, medical examination, electrocardiogram (ECG), serum chemistry, hematology, coagulation urinalysis, and serology. * NOTE- Additional criteria apply, please contact the investigator for more information
Exclusion criteria
* The participant has a current clinically significant DSM-5 diagnosis other than schizophrenia (has a primary current diagnosis other than schizophrenia or a comorbid diagnosis that is primarily responsible for the current symptoms and functional impairment). * The participant has a known history of the following: (a) borderline personality disorder, antisocial personality disorder, or bipolar disorder; (b) traumatic brain injury causing ongoing cognitive difficulties, Alzheimer's disease, or another form of dementia, or any chronic organic disease of the central nervous system; and (c) intellectual disability of a severity that would impact ability to participate in the study. * The participant was hospitalized for \>14 days (with the exception of social or administrative hospitalization) in the current exacerbation episode prior to screening. * The participant has a significant risk of violent behavior based on the participant's medical history or investigator's judgment. * The participant has a significant risk of committing suicide based on the participant's medical history or C-SSRS, and the investigator's judgment. * The participant is currently using an LAI antipsychotic or is still under the coverage period of the specific LAI at time of screening. * The participant has taken clozapine or has received electroconvulsive therapy within the last 12 months prior to screening. * The participant is currently receiving daily oral olanzapine at a dose \>20 mg/day. * The participant has current or a history of known hypersensitivity to olanzapine or any of the excipients of TV-44749 or the oral formulation of olanzapine. * The participant has had a significant sedation or delirium after antipsychotic treatment according to medical and psychiatric history and as judged by the investigator or suffered from delirium due to a medical condition. * The participant has a non-fasting glucose level of ≥200 mg/dL at screening * The participant meets criteria for moderate to severe substance use disorder (based on DSM-5 criteria) within the past 6 months (excluding those related to caffeine or nicotine) * NOTE- Additional criteria apply, please contact the investigator for more information
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Period: Change in the Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 8 | Baseline, Week 8 | The PANSS is a 30-item scale used to evaluate positive and negative symptoms of schizophrenia. The PANSS was used to identify the presence and severity of psychopathology symptoms, the relationship of these symptoms to one another, and the global psychopathology. Each item was scored on a 7-point scale ranging from 1 (absent) to 7 (extreme). The positive symptom scale includes 7 items with a maximum score of 49; the negative symptom scale includes 7 items with a maximum score of 49; and the general psychopathology scale includes 16 items with a maximum score of 112. The total score was the sum of 30-item scale, ranging from 30 (absent) to 210 (extreme), with a higher score indicating greater severity of symptoms. Least square (LS) mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PANSS total score at baseline as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Period: Change in Clinical Global Impression-Severity (CGI-S) Scale Score From Baseline to Week 8 | Baseline, Week 8 | The CGI-S is a 7-point scale that assess the participant's current severity of illness on a scale of 1 to 7, where 1=normal/not at all ill, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill patients. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and CGI-S score at baseline as covariates. |
| Double-blind Period: Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 8 | Baseline, Week 8 | The PSP is a clinician-rated instrument that measures personal and social functioning in participants with schizophrenia. The PSP is a 100-point single-item rating scale, divided into 10 equal intervals, where 0 (grossly impaired functioning) to 100 (excellent functioning). The score was based on the assessment of participant's functioning in 4 categories: 1) socially useful activities, including work and study; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviors. Higher scores represented better personal and social functioning, with ratings from 91 to 100 indicating more than adequate functioning, while scores under 30 indicating poor functioning that required intensive supervision. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PSP score at baseline as covariates. |
| Double-blind Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Week 8 | An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. The SAEs 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 the Reported AE section. |
| Integrated Study Period: Number of Participants With AEs and SAEs | Baseline up to Week 60 | An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. The SAEs 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 the Reported AE section. |
| Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Baseline, Weeks 1, 2, and 4 | The PANSS is a 30-item scale used to evaluate positive and negative symptoms of schizophrenia. The PANSS was used to identify the presence and severity of psychopathology symptoms, the relationship of these symptoms to one another, and the global psychopathology. Each item was scored on a 7-point scale ranging from 1 (absent) to 7 (extreme). The positive symptom scale includes 7 items with a maximum score of 49; the negative symptom scale includes 7 items with a maximum score of 49; and the general psychopathology scale includes 16 items with a maximum score of 112. The total score was the sum of 30-item scale, ranging from 30 (absent) to 210 (extreme), with a higher score indicating greater severity of symptoms. Least square (LS) mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PANSS total score at baseline as covariates. |
| Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8 | Weeks 4 and 8 | The CGI-I is a 7-point scale that permits a global evaluation of the participant's overall improvement in symptoms on a scale of 1 to 7, where 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and CGI-I score at baseline as covariates. |
| Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Baseline, Weeks 1, 2, and 4 | The CGI-S is a 7-point scale that assess the participant's current severity of illness on a scale of 1 to 7, where 1=normal/not at all ill, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill patients. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and CGI-S score at baseline as covariates. |
| Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Weeks 2, 4, and 8 | The PGI-I scale is a 1-item participant-rated instrument that measures improvement of the participant's disease. The participant rated the perceived change in his/her condition in response to therapy on a scale of 1 to 7, where 1=very much better, 2=much better, 3=a little better, 4=no change, 5=a little worse, 6=much worse, 7=very much worse. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PGI-I score at baseline as covariates. |
| Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8 | Baseline, Weeks 4 and 8 | The SQLS Revision 4 was administered to capture quality of life. The 33-item measure yields subscales pertaining to psychosocial (20 items) and cognition/vitality factors (13 items). Each item was 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 from 0 (best health status) to 100 (worst health status) scale, with higher scores indicating comparatively lower quality of life. |
| Double-blind Period: Change in PSP Score From Baseline to Week 4 | Baseline, Week 4 | The PSP is a clinician-rated instrument that measures personal and social functioning in participants with schizophrenia. The PSP is a 100-point single-item rating scale, divided into 10 equal intervals, where 0 (grossly impaired functioning) to 100 (excellent functioning). The score was based on the assessment of participant's functioning in 4 categories: 1) socially useful activities, including work and study; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviors. Higher scores represented better personal and social functioning, with ratings from 91 to 100 indicating more than adequate functioning, while scores under 30 indicating functioning so poor that intensive supervision was required. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PSP score at baseline as covariates. |
| Double-blind Period: Number of Participants Receiving At Least 1 Concomitant Medication | Baseline up to Week 8 | Concomitant medications included all medications taken while the participant was treated with the study drug. Any concomitant medication received by the participant for AEs was recorded on the case report form (CRF). Concomitant medications included: zolpidem, zopiclone, zaleplon, or diphenhydramine for insomnia; benztropine, trihexyphenidyl, or diphenhydramine for parkinsonian symptoms; propranolol and benzodiazepines for akathisia; lorazepam on an as-needed basis for indications other than akathisia (for example, anxiety); and antihistamine and anticholinergic drugs for agitation and insomnia. |
| Integrated Study Period: Number of Participants Receiving At Least 1 Concomitant Medication | Baseline up to Week 60 | Concomitant medications included all medications taken while the participant was treated with the study drug. Any concomitant medication received by the participant for AEs was recorded on the CRF. Concomitant medications included: zolpidem, zopiclone, zaleplon, or diphenhydramine for insomnia; benztropine, trihexyphenidyl, or diphenhydramine for parkinsonian symptoms; propranolol and benzodiazepines for akathisia; lorazepam on an as-needed basis for indications other than akathisia (for example, anxiety); and antihistamine and anticholinergic drugs for agitation and insomnia. |
| Double-blind Period: Change From Baseline to Week 8 in Abnormal Involuntary Movement Scale (AIMS) Total Score | Baseline, Week 8 | 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. AIMS total score was calculated as a sum of items 1 through 7. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated from 0 (none) to 4 (severe) The AIMS total score for Items 1-7 ranged from 0 (no dyskinesia) to 28 (severe dyskinesia) with a higher score indicating greater severity of the condition. |
| Integrated Study Period: Change From Baseline to Week 60 in AIMS Total Score | Baseline, Week 60 | 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. AIMS total score was calculated as a sum of items 1 through 7. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated from 0 (none) to 4 (severe) The AIMS total score for Items 1-7 ranged from 0 (no dyskinesia) to 28 (severe dyskinesia) with a higher score indicating greater severity of the condition. |
| Double-blind Period: Change From Baseline to Week 8 in Simpson-Angus Scale (SAS) Mean Score | Baseline, Week 8 | 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 \[normal\] to 4 \[severe\]). The mean score was calculated by adding the individual item scores and dividing by 10, ranging from 0 (normal) to 4 (severe) with a higher score indicating greater severity of symptoms. |
| Integrated Study Period: Change From Baseline to Week 60 in SAS Mean Score | Baseline, Week 60 | 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 \[normal\] to 4 \[severe\]). The mean score was calculated by adding the individual item scores and dividing by 10, ranging from 0 (normal) to 4 (severe) with a higher score indicating greater severity of symptoms. |
| Double-blind Period: Change From Baseline to Week 8 in Barnes Akathisia Rating Scale (BARS) Total Score | Baseline, Week 8 | The BARS is an instrument that assesses the severity of drug-induced akathisia. The BARS included 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) to 3 (most severe) and summed up yielding a total score ranging from 0 (normal) to 9 (most severe). Higher scores indicated greater severity of akathisia. |
| Integrated Study Period: Change From Baseline to Week 60 in BARS Total Score | Baseline, Week 60 | The BARS is an instrument that assesses the severity of drug-induced akathisia. The BARS included 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) to 3 (most severe) and summed up yielding a total score ranging from 0 (normal) to 9 (most severe). Higher scores indicated greater severity of akathisia. |
| Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Baseline up to Week 8 | The C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. 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, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent. |
| Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | Baseline up to Week 60 | The C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. 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, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent. |
| Double-blind Period: Change From Baseline to Week 8 in Calgary Depression Scale for Schizophrenia (CDSS) Score | Baseline, Week 8 | The CDSS is specifically designed to assess the level of depression separate from the positive, negative, and extrapyramidal symptoms in schizophrenia. This clinician-administered instrument consisted of 9 items, each rated on a 4-point scale from 0 (absent) to 3 (severe) that are added together to form the CDSS depression total score for the participant ranging from 0 (absent) to 27 (severe) with higher scores indicating a higher severity of depression. |
| Integrated Study Period: Change From Baseline to Week 60 in CDSS Score | Baseline, Week 60 | The CDSS is specifically designed to assess the level of depression separate from the positive, negative, and extrapyramidal symptoms in schizophrenia. This clinician-administered instrument consisted of 9 items, each rated on a 4-point scale from 0 (absent) to 3 (severe) that are added together to form the CDSS depression total score for the participant ranging from 0 (absent) to 27 (severe) with higher scores indicating a higher severity of depression. |
Countries
Bulgaria, China, Romania, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORTeva Medical Expert, MD
Teva Branded Pharmaceutical Products R&D LLC
Participant flow
Recruitment details
The study comprised 2 periods: Period 1 (double-blind, placebo-controlled, efficacy and safety period \[acute treatment phase\]) and Period 2 (open-label safety period \[long-term safety phase\]).
Pre-assignment details
Per planned analysis, the safety analysis was performed separately for Period 1 and for the integrated trial period. Integrated trial period included all participants who received 1 of the 3 TV-44749 treatments in Period 1 and all randomized participants to Period 2 who received at least 1 dose of TV-44749.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to TV-44749 SC once monthly over 8 weeks in double-blind period. | 168 |
| TV-44749 318 mg Participants received TV-44749 extended-release injectable suspension at a dose of 318 mg SC once monthly over 8 weeks in double-blind period and up to an additional 48 weeks in open-label period, for a total of 56 weeks. | 169 |
| TV-44749 425 mg Participants received TV-44749 extended-release injectable suspension at a dose of 425 mg SC once monthly over 8 weeks in double-blind period and up to an additional 48 weeks in open-label period, for a total of 56 weeks. | 169 |
| TV-44749 531 mg Participants received TV-44749 extended-release injectable suspension at a dose of 531 mg SC once monthly over 8 weeks in double-blind period and up to an additional 48 weeks in open-label period, for a total of 56 weeks. | 169 |
| Total | 675 |
Baseline characteristics
| Characteristic | Total | Placebo | TV-44749 318 mg | TV-44749 425 mg | TV-44749 531 mg |
|---|---|---|---|---|---|
| Age, Customized 18 - 30 years | 90 Participants | 16 Participants | 28 Participants | 22 Participants | 24 Participants |
| Age, Customized >30 - 45 years | 274 Participants | 86 Participants | 59 Participants | 65 Participants | 64 Participants |
| Age, Customized >45 - 65 years | 311 Participants | 66 Participants | 82 Participants | 82 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 132 Participants | 28 Participants | 38 Participants | 34 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 539 Participants | 139 Participants | 130 Participants | 135 Participants | 135 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 4 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 12 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 462 Participants | 121 Participants | 116 Participants | 106 Participants | 119 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not reported | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other | 6 Participants | 5 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 187 Participants | 36 Participants | 51 Participants | 56 Participants | 44 Participants |
| Sex: Female, Male Female | 168 Participants | 42 Participants | 42 Participants | 42 Participants | 42 Participants |
| Sex: Female, Male Male | 507 Participants | 126 Participants | 127 Participants | 127 Participants | 127 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 168 | 0 / 169 | 0 / 169 | 0 / 169 | 2 / 209 | 0 / 204 | 1 / 198 |
| other Total, other adverse events | 38 / 167 | 82 / 163 | 99 / 168 | 98 / 169 | 105 / 204 | 113 / 203 | 113 / 197 |
| serious Total, serious adverse events | 3 / 167 | 4 / 163 | 1 / 168 | 2 / 169 | 15 / 204 | 8 / 203 | 13 / 197 |
Outcome results
Primary
Double-blind Period: Change in the Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 8
The PANSS is a 30-item scale used to evaluate positive and negative symptoms of schizophrenia. The PANSS was used to identify the presence and severity of psychopathology symptoms, the relationship of these symptoms to one another, and the global psychopathology. Each item was scored on a 7-point scale ranging from 1 (absent) to 7 (extreme). The positive symptom scale includes 7 items with a maximum score of 49; the negative symptom scale includes 7 items with a maximum score of 49; and the general psychopathology scale includes 16 items with a maximum score of 112. The total score was the sum of 30-item scale, ranging from 30 (absent) to 210 (extreme), with a higher score indicating greater severity of symptoms. Least square (LS) mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PANSS total score at baseline as covariates.
Time frame: Baseline, Week 8
Population: Full Analysis Set included all participants randomized to study arms in Period 1 regardless of the actual treatment the participants received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change in the Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 8 | -12.17 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in the Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 8 | -21.91 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in the Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 8 | -23.44 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in the Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 8 | -21.93 units on a scale |
Comparison: Mixed model for repeated measures fitted to 200 multiply imputed datasets generated in accordance with the estimand. Treatment group LS mean, 95% confidence intervals, and two-sided p values were pooled across imputations using Rubin's rules.p-value: <0.000195% CI: [-13.6, -5.89]Mixed Models Analysis
Comparison: Mixed model for repeated measures fitted to 200 multiply imputed datasets generated in accordance with the estimand. Treatment group LS mean, 95% confidence intervals, and two-sided p values were pooled across imputations using Rubin's rules.p-value: <0.000195% CI: [-15.01, -7.53]Mixed Models Analysis
Comparison: Mixed model for repeated measures fitted to 200 multiply imputed datasets generated in accordance with the estimand. Treatment group LS mean, 95% confidence intervals, and two-sided p values were pooled across imputations using Rubin's rules.p-value: <0.000195% CI: [-13.5, -6.02]Mixed Models Analysis
Secondary
Double-blind Period: Change From Baseline to Week 8 in Abnormal Involuntary Movement Scale (AIMS) Total Score
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. AIMS total score was calculated as a sum of items 1 through 7. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated from 0 (none) to 4 (severe) The AIMS total score for Items 1-7 ranged from 0 (no dyskinesia) to 28 (severe dyskinesia) with a higher score indicating greater severity of the condition.
Time frame: Baseline, Week 8
Population: Safety Analysis Set for Period 1 included all randomized participants who received at least 1 dose of TV-44749 or placebo. Participants were included in the treatment group corresponding to what they actually received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change From Baseline to Week 8 in Abnormal Involuntary Movement Scale (AIMS) Total Score | -0.1 units on a scale | Standard Deviation 0.83 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change From Baseline to Week 8 in Abnormal Involuntary Movement Scale (AIMS) Total Score | -0.1 units on a scale | Standard Deviation 0.81 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change From Baseline to Week 8 in Abnormal Involuntary Movement Scale (AIMS) Total Score | 0.0 units on a scale | Standard Deviation 0.64 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change From Baseline to Week 8 in Abnormal Involuntary Movement Scale (AIMS) Total Score | 0.0 units on a scale | Standard Deviation 0.5 |
Secondary
Double-blind Period: Change From Baseline to Week 8 in Barnes Akathisia Rating Scale (BARS) Total Score
The BARS is an instrument that assesses the severity of drug-induced akathisia. The BARS included 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) to 3 (most severe) and summed up yielding a total score ranging from 0 (normal) to 9 (most severe). Higher scores indicated greater severity of akathisia.
Time frame: Baseline, Week 8
Population: Safety Analysis Set for Period 1 included all randomized participants who received at least 1 dose of TV-44749 or placebo. Participants were included in the treatment group corresponding to what they actually received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change From Baseline to Week 8 in Barnes Akathisia Rating Scale (BARS) Total Score | -0.1 units on a scale | Standard Deviation 0.56 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change From Baseline to Week 8 in Barnes Akathisia Rating Scale (BARS) Total Score | -0.1 units on a scale | Standard Deviation 0.66 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change From Baseline to Week 8 in Barnes Akathisia Rating Scale (BARS) Total Score | 0.0 units on a scale | Standard Deviation 0.48 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change From Baseline to Week 8 in Barnes Akathisia Rating Scale (BARS) Total Score | -0.1 units on a scale | Standard Deviation 0.5 |
Secondary
Double-blind Period: Change From Baseline to Week 8 in Calgary Depression Scale for Schizophrenia (CDSS) Score
The CDSS is specifically designed to assess the level of depression separate from the positive, negative, and extrapyramidal symptoms in schizophrenia. This clinician-administered instrument consisted of 9 items, each rated on a 4-point scale from 0 (absent) to 3 (severe) that are added together to form the CDSS depression total score for the participant ranging from 0 (absent) to 27 (severe) with higher scores indicating a higher severity of depression.
Time frame: Baseline, Week 8
Population: Safety Analysis Set for Period 1 included all randomized participants who received at least 1 dose of TV-44749 or placebo. Participants were included in the treatment group corresponding to what they actually received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change From Baseline to Week 8 in Calgary Depression Scale for Schizophrenia (CDSS) Score | -1.1 units on a scale | Standard Deviation 3.16 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change From Baseline to Week 8 in Calgary Depression Scale for Schizophrenia (CDSS) Score | -2.1 units on a scale | Standard Deviation 3.95 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change From Baseline to Week 8 in Calgary Depression Scale for Schizophrenia (CDSS) Score | -1.7 units on a scale | Standard Deviation 3.17 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change From Baseline to Week 8 in Calgary Depression Scale for Schizophrenia (CDSS) Score | -2.0 units on a scale | Standard Deviation 3.77 |
Secondary
Double-blind Period: Change From Baseline to Week 8 in Simpson-Angus Scale (SAS) Mean Score
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 \[normal\] to 4 \[severe\]). The mean score was calculated by adding the individual item scores and dividing by 10, ranging from 0 (normal) to 4 (severe) with a higher score indicating greater severity of symptoms.
Time frame: Baseline, Week 8
Population: Safety Analysis Set for Period 1 included all randomized participants who received at least 1 dose of TV-44749 or placebo. Participants were included in the treatment group corresponding to what they actually received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change From Baseline to Week 8 in Simpson-Angus Scale (SAS) Mean Score | -0.02 units on a scale | Standard Deviation 0.142 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change From Baseline to Week 8 in Simpson-Angus Scale (SAS) Mean Score | -0.02 units on a scale | Standard Deviation 0.107 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change From Baseline to Week 8 in Simpson-Angus Scale (SAS) Mean Score | 0.00 units on a scale | Standard Deviation 0.065 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change From Baseline to Week 8 in Simpson-Angus Scale (SAS) Mean Score | -0.01 units on a scale | Standard Deviation 0.073 |
Secondary
Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4
The CGI-S is a 7-point scale that assess the participant's current severity of illness on a scale of 1 to 7, where 1=normal/not at all ill, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill patients. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and CGI-S score at baseline as covariates.
Time frame: Baseline, Weeks 1, 2, and 4
Population: Full Analysis Set included all participants randomized to Period 1 regardless of the actual treatment the participants received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 2 | -0.42 units on a scale |
| Double-blind: Placebo | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 4 | -0.54 units on a scale |
| Double-blind: Placebo | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 1 | -0.27 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 4 | -0.86 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 1 | -0.33 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 2 | -0.56 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 2 | -0.59 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 1 | -0.33 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 4 | -0.79 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 4 | -0.76 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 2 | -0.48 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4 | Change at Week 1 | -0.23 units on a scale |
Secondary
Double-blind Period: Change in Clinical Global Impression-Severity (CGI-S) Scale Score From Baseline to Week 8
The CGI-S is a 7-point scale that assess the participant's current severity of illness on a scale of 1 to 7, where 1=normal/not at all ill, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill patients. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and CGI-S score at baseline as covariates.
Time frame: Baseline, Week 8
Population: Full Analysis Set included all participants randomized to study arms in Period 1 regardless of the actual treatment the participants received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change in Clinical Global Impression-Severity (CGI-S) Scale Score From Baseline to Week 8 | -0.72 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in Clinical Global Impression-Severity (CGI-S) Scale Score From Baseline to Week 8 | -1.25 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in Clinical Global Impression-Severity (CGI-S) Scale Score From Baseline to Week 8 | -1.33 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in Clinical Global Impression-Severity (CGI-S) Scale Score From Baseline to Week 8 | -1.19 units on a scale |
Comparison: Mixed model for repeated measures fitted to 200 multiply imputed datasets generated in accordance with the estimand. Treatment group LS mean, 95% confidence intervals, and two-sided p values were pooled across imputations using Rubin's rules.p-value: <0.000195% CI: [-0.75, -0.31]Mixed Models Analysis
Comparison: Mixed model for repeated measures fitted to 200 multiply imputed datasets generated in accordance with the estimand. Treatment group LS mean, 95% confidence intervals, and two-sided p values were pooled across imputations using Rubin's rules.p-value: <0.000195% CI: [-0.82, -0.39]Mixed Models Analysis
Comparison: Mixed model for repeated measures fitted to 200 multiply imputed datasets generated in accordance with the estimand. Treatment group LS mean, 95% confidence intervals, and two-sided p values were pooled across imputations using Rubin's rules.p-value: <0.000195% CI: [-0.68, -0.25]Mixed Models Analysis
Secondary
Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4
The PANSS is a 30-item scale used to evaluate positive and negative symptoms of schizophrenia. The PANSS was used to identify the presence and severity of psychopathology symptoms, the relationship of these symptoms to one another, and the global psychopathology. Each item was scored on a 7-point scale ranging from 1 (absent) to 7 (extreme). The positive symptom scale includes 7 items with a maximum score of 49; the negative symptom scale includes 7 items with a maximum score of 49; and the general psychopathology scale includes 16 items with a maximum score of 112. The total score was the sum of 30-item scale, ranging from 30 (absent) to 210 (extreme), with a higher score indicating greater severity of symptoms. Least square (LS) mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PANSS total score at baseline as covariates.
Time frame: Baseline, Weeks 1, 2, and 4
Population: Full Analysis Set included all participants randomized to study arms in Period 1 regardless of the actual treatment the participants received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 1 | -5.74 units on a scale |
| Double-blind: Placebo | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 4 | -9.40 units on a scale |
| Double-blind: Placebo | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 2 | -7.95 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 2 | -11.02 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 4 | -15.27 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 1 | -7.54 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 4 | -15.91 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 1 | -7.29 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 2 | -11.25 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 1 | -6.22 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 4 | -14.74 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4 | Change at Week 2 | -10.05 units on a scale |
Secondary
Double-blind Period: Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 8
The PSP is a clinician-rated instrument that measures personal and social functioning in participants with schizophrenia. The PSP is a 100-point single-item rating scale, divided into 10 equal intervals, where 0 (grossly impaired functioning) to 100 (excellent functioning). The score was based on the assessment of participant's functioning in 4 categories: 1) socially useful activities, including work and study; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviors. Higher scores represented better personal and social functioning, with ratings from 91 to 100 indicating more than adequate functioning, while scores under 30 indicating poor functioning that required intensive supervision. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PSP score at baseline as covariates.
Time frame: Baseline, Week 8
Population: Full Analysis Set included all participants randomized to study arms in Period 1 regardless of the actual treatment the participants received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 8 | 5.59 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 8 | 10.31 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 8 | 8.83 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 8 | 10.59 units on a scale |
Comparison: Mixed model for repeated measures fitted to 200 multiply imputed datasets generated in accordance with the estimand. Treatment group LS mean, 95% confidence intervals, and two-sided p values were pooled across imputations using Rubin's rules.p-value: 0.001195% CI: [2.05, 7.4]Mixed Models Analysis
Comparison: Mixed model for repeated measures fitted to 200 multiply imputed datasets generated in accordance with the estimand. Treatment group LS mean, 95% confidence intervals, and two-sided p values were pooled across imputations using Rubin's rules.p-value: 0.016795% CI: [0.59, 5.89]Mixed Models Analysis
Comparison: Mixed model for repeated measures fitted to 200 multiply imputed datasets generated in accordance with the estimand. Treatment group LS mean, 95% confidence intervals, and two-sided p values were pooled across imputations using Rubin's rules.p-value: 0.000795% CI: [2.35, 7.66]Mixed Models Analysis
Secondary
Double-blind Period: Change in PSP Score From Baseline to Week 4
The PSP is a clinician-rated instrument that measures personal and social functioning in participants with schizophrenia. The PSP is a 100-point single-item rating scale, divided into 10 equal intervals, where 0 (grossly impaired functioning) to 100 (excellent functioning). The score was based on the assessment of participant's functioning in 4 categories: 1) socially useful activities, including work and study; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviors. Higher scores represented better personal and social functioning, with ratings from 91 to 100 indicating more than adequate functioning, while scores under 30 indicating functioning so poor that intensive supervision was required. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PSP score at baseline as covariates.
Time frame: Baseline, Week 4
Population: Full Analysis Set included all participants randomized to Period 1 regardless of the actual treatment the participants received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change in PSP Score From Baseline to Week 4 | 3.22 units on a scale |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in PSP Score From Baseline to Week 4 | 6.14 units on a scale |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in PSP Score From Baseline to Week 4 | 4.46 units on a scale |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in PSP Score From Baseline to Week 4 | 4.88 units on a scale |
Secondary
Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8
The SQLS Revision 4 was administered to capture quality of life. The 33-item measure yields subscales pertaining to psychosocial (20 items) and cognition/vitality factors (13 items). Each item was 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 from 0 (best health status) to 100 (worst health status) scale, with higher scores indicating comparatively lower quality of life.
Time frame: Baseline, Weeks 4 and 8
Population: Full Analysis Set included all participants randomized to Period 1 regardless of the actual treatment the participants received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8 | Change at Week 4 | -5.63 units on a scale | Standard Error 1.59 |
| Double-blind: Placebo | Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8 | Change at Week 8 | -6.43 units on a scale | Standard Error 1.79 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8 | Change at Week 4 | -8.47 units on a scale | Standard Error 1.62 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8 | Change at Week 8 | -10.42 units on a scale | Standard Error 1.81 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8 | Change at Week 8 | -11.82 units on a scale | Standard Error 1.75 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8 | Change at Week 4 | -7.16 units on a scale | Standard Error 1.57 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8 | Change at Week 8 | -12.08 units on a scale | Standard Error 1.77 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8 | Change at Week 4 | -8.45 units on a scale | Standard Error 1.58 |
Secondary
Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8
The CGI-I is a 7-point scale that permits a global evaluation of the participant's overall improvement in symptoms on a scale of 1 to 7, where 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and CGI-I score at baseline as covariates.
Time frame: Weeks 4 and 8
Population: Full Analysis Set included all participants randomized to study arms in Period 1 regardless of the actual treatment the participants received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8 | Week 4 | 3.42 units on a scale | Standard Error 0.09 |
| Double-blind: Placebo | Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8 | Week 8 | 3.31 units on a scale | Standard Error 0.1 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8 | Week 8 | 2.64 units on a scale | Standard Error 0.1 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8 | Week 4 | 2.97 units on a scale | Standard Error 0.09 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8 | Week 4 | 3.00 units on a scale | Standard Error 0.08 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8 | Week 8 | 2.51 units on a scale | Standard Error 0.1 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8 | Week 4 | 2.97 units on a scale | Standard Error 0.08 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8 | Week 8 | 2.56 units on a scale | Standard Error 0.1 |
Secondary
Double-blind Period: Number of Participants Receiving At Least 1 Concomitant Medication
Concomitant medications included all medications taken while the participant was treated with the study drug. Any concomitant medication received by the participant for AEs was recorded on the case report form (CRF). Concomitant medications included: zolpidem, zopiclone, zaleplon, or diphenhydramine for insomnia; benztropine, trihexyphenidyl, or diphenhydramine for parkinsonian symptoms; propranolol and benzodiazepines for akathisia; lorazepam on an as-needed basis for indications other than akathisia (for example, anxiety); and antihistamine and anticholinergic drugs for agitation and insomnia.
Time frame: Baseline up to Week 8
Population: Safety Analysis Set for Period 1 included all randomized participants who received at least 1 dose of TV-44749 or placebo. Participants were included in the treatment group corresponding to what they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind: Placebo | Double-blind Period: Number of Participants Receiving At Least 1 Concomitant Medication | 138 Participants |
| Double-blind: TV-44749 318 mg | Double-blind Period: Number of Participants Receiving At Least 1 Concomitant Medication | 128 Participants |
| Double-blind: TV-44749 425 mg | Double-blind Period: Number of Participants Receiving At Least 1 Concomitant Medication | 128 Participants |
| Double-blind: TV-44749 531 mg | Double-blind Period: Number of Participants Receiving At Least 1 Concomitant Medication | 141 Participants |
Secondary
Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. 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, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent.
Time frame: Baseline up to Week 8
Population: Safety Analysis Set for Period 1 included all randomized participants who received at least 1 dose of TV-44749 or placebo. Participants were included in the treatment group corresponding to what they actually received.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | No | 154 Participants |
| Double-blind: Placebo | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Missing | 4 Participants |
| Double-blind: Placebo | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Yes | 9 Participants |
| Double-blind: TV-44749 318 mg | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | No | 149 Participants |
| Double-blind: TV-44749 318 mg | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Missing | 6 Participants |
| Double-blind: TV-44749 318 mg | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Yes | 8 Participants |
| Double-blind: TV-44749 425 mg | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Yes | 9 Participants |
| Double-blind: TV-44749 425 mg | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | No | 156 Participants |
| Double-blind: TV-44749 425 mg | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Missing | 3 Participants |
| Double-blind: TV-44749 531 mg | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | No | 165 Participants |
| Double-blind: TV-44749 531 mg | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Missing | 0 Participants |
| Double-blind: TV-44749 531 mg | Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | Yes | 4 Participants |
Secondary
Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. The SAEs 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 TEAE was defined as an AE that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section.
Time frame: Baseline up to Week 8
Population: Safety Analysis Set for Period 1 included all randomized participants who received at least 1 dose of TV-44749 or placebo. Participants were included in the treatment group corresponding to what they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 3 Participants |
| Double-blind: Placebo | Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 84 Participants |
| Double-blind: TV-44749 318 mg | Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 4 Participants |
| Double-blind: TV-44749 318 mg | Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 112 Participants |
| Double-blind: TV-44749 425 mg | Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 117 Participants |
| Double-blind: TV-44749 425 mg | Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 1 Participants |
| Double-blind: TV-44749 531 mg | Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 2 Participants |
| Double-blind: TV-44749 531 mg | Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 126 Participants |
Secondary
Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8
The PGI-I scale is a 1-item participant-rated instrument that measures improvement of the participant's disease. The participant rated the perceived change in his/her condition in response to therapy on a scale of 1 to 7, where 1=very much better, 2=much better, 3=a little better, 4=no change, 5=a little worse, 6=much worse, 7=very much worse. LS mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PGI-I score at baseline as covariates.
Time frame: Weeks 2, 4, and 8
Population: Full Analysis Set included all participants randomized to Period 1 regardless of the actual treatment the participants received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind: Placebo | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 8 | 2.99 units on a scale | Standard Error 0.13 |
| Double-blind: Placebo | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 4 | 3.24 units on a scale | Standard Error 0.12 |
| Double-blind: Placebo | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 2 | 3.30 units on a scale | Standard Error 0.11 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 4 | 2.79 units on a scale | Standard Error 0.12 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 2 | 2.95 units on a scale | Standard Error 0.11 |
| Double-blind: TV-44749 318 mg | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 8 | 2.46 units on a scale | Standard Error 0.13 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 2 | 2.92 units on a scale | Standard Error 0.11 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 4 | 2.92 units on a scale | Standard Error 0.12 |
| Double-blind: TV-44749 425 mg | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 8 | 2.49 units on a scale | Standard Error 0.12 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 4 | 2.81 units on a scale | Standard Error 0.12 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 8 | 2.43 units on a scale | Standard Error 0.12 |
| Double-blind: TV-44749 531 mg | Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8 | Week 2 | 3.16 units on a scale | Standard Error 0.11 |
Secondary
Integrated Study Period: Change From Baseline to the End of Treatment (EOT) in AIMS Total Score
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. AIMS total score was calculated as a sum of items 1 through 7. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated from 0 (none) to 4 (severe) The AIMS total score for Items 1-7 ranged from 0 (no dyskinesia) to 28 (severe dyskinesia) with a higher score indicating greater severity of the condition.
Time frame: Baseline, EOT (up to Week 56)
Population: Safety Analysis Set for integrated study period included all participants in the safety analysis set of period 1 that received 1 of the 3 TV-44749 treatments groups and all randomized participants to Period 2 who received at least 1 dose of TV-44749. Participants were included in their randomized treatment groups regardless of the actual treatment received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Integrated Study Period: Change From Baseline to the End of Treatment (EOT) in AIMS Total Score | -0.10 units on a scale | Standard Deviation 1.213 |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Change From Baseline to the End of Treatment (EOT) in AIMS Total Score | -0.10 units on a scale | Standard Deviation 0.416 |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Change From Baseline to the End of Treatment (EOT) in AIMS Total Score | -0.09 units on a scale | Standard Deviation 0.793 |
Secondary
Integrated Study Period: Change From Baseline to the EOT in BARS Total Score
The BARS is an instrument that assesses the severity of drug-induced akathisia. The BARS included 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) to 3 (most severe) and summed up yielding a total score ranging from 0 (normal) to 9 (most severe). Higher scores indicated greater severity of akathisia.
Time frame: Baseline, EOT (up to Week 56)
Population: Safety Analysis Set for integrated study period included all participants in the safety analysis set of period 1 that received 1 of the 3 TV-44749 treatments groups and all randomized participants to Period 2 who received at least 1 dose of TV-44749. Participants were included in their randomized treatment groups regardless of the actual treatment received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Integrated Study Period: Change From Baseline to the EOT in BARS Total Score | -0.1 units on a scale | Standard Deviation 0.72 |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Change From Baseline to the EOT in BARS Total Score | -0.1 units on a scale | Standard Deviation 0.52 |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Change From Baseline to the EOT in BARS Total Score | -0.1 units on a scale | Standard Deviation 0.82 |
Secondary
Integrated Study Period: Change From Baseline to the EOT in CDSS Score
The CDSS is specifically designed to assess the level of depression separate from the positive, negative, and extrapyramidal symptoms in schizophrenia. This clinician-administered instrument consisted of 9 items, each rated on a 4-point scale from 0 (absent) to 3 (severe) that are added together to form the CDSS depression total score for the participant ranging from 0 (absent) to 27 (severe) with higher scores indicating a higher severity of depression.
Time frame: Baseline, EOT (up to Week 56)
Population: Safety Analysis Set for integrated study period included all participants in the safety analysis set of period 1 that received 1 of the 3 TV-44749 treatments groups and all randomized participants to Period 2 who received at least 1 dose of TV-44749. Participants were included in their randomized treatment groups regardless of the actual treatment received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Integrated Study Period: Change From Baseline to the EOT in CDSS Score | -2.2 units on a scale | Standard Deviation 4.08 |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Change From Baseline to the EOT in CDSS Score | -1.6 units on a scale | Standard Deviation 3.29 |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Change From Baseline to the EOT in CDSS Score | -1.5 units on a scale | Standard Deviation 3.72 |
Secondary
Integrated Study Period: Change From Baseline to the EOT in SAS Mean Score
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 \[normal\] to 4 \[severe\]). The mean score was calculated by adding the individual item scores and dividing by 10, ranging from 0 (normal) to 4 (severe) with a higher score indicating greater severity of symptoms.
Time frame: Baseline, EOT (up to Week 56)
Population: Safety Analysis Set for integrated study period included all participants in the safety analysis set of period 1 that received 1 of the 3 TV-44749 treatments groups and all randomized participants to Period 2 who received at least 1 dose of TV-44749. Participants were included in their randomized treatment groups regardless of the actual treatment received. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind: Placebo | Integrated Study Period: Change From Baseline to the EOT in SAS Mean Score | -0.03 units on a scale | Standard Deviation 0.154 |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Change From Baseline to the EOT in SAS Mean Score | -0.01 units on a scale | Standard Deviation 0.049 |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Change From Baseline to the EOT in SAS Mean Score | -0.01 units on a scale | Standard Deviation 0.077 |
Secondary
Integrated Study Period: Number of Participants Receiving At Least 1 Concomitant Medication
Concomitant medications included all medications taken while the participant was treated with the study drug. Any concomitant medication received by the participant for AEs was recorded on the CRF. Concomitant medications included: zolpidem, zopiclone, zaleplon, or diphenhydramine for insomnia; benztropine, trihexyphenidyl, or diphenhydramine for parkinsonian symptoms; propranolol and benzodiazepines for akathisia; lorazepam on an as-needed basis for indications other than akathisia (for example, anxiety); and antihistamine and anticholinergic drugs for agitation and insomnia.
Time frame: Baseline up to Week 60
Population: Safety Analysis Set for integrated study period included all participants in the safety analysis set of period 1 that received 1 of the 3 TV-44749 treatments groups and all randomized participants to Period 2 who received at least 1 dose of TV-44749. Participants were included in their randomized treatment groups regardless of the actual treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind: Placebo | Integrated Study Period: Number of Participants Receiving At Least 1 Concomitant Medication | 148 Participants |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Number of Participants Receiving At Least 1 Concomitant Medication | 142 Participants |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Number of Participants Receiving At Least 1 Concomitant Medication | 156 Participants |
Secondary
Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS
The C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. 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, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent.
Time frame: Baseline up to Week 60
Population: Safety Analysis Set for integrated study period included all participants in the safety analysis set of period 1 that received 1 of the 3 TV-44749 treatments groups and all randomized participants to Period 2 who received at least 1 dose of TV-44749. Participants were included in their randomized treatment groups regardless of the actual treatment received.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind: Placebo | Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | Missing | 6 Participants |
| Double-blind: Placebo | Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | No | 184 Participants |
| Double-blind: Placebo | Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | Yes | 14 Participants |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | Missing | 4 Participants |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | No | 183 Participants |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | Yes | 16 Participants |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | No | 186 Participants |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | Yes | 11 Participants |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS | Missing | 0 Participants |
Secondary
Integrated Study Period: Number of Participants With TEAEs and SAEs
An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. The SAEs 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 TEAE was defined as an AE that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section.
Time frame: Baseline up to Week 60
Population: Safety Analysis Set for integrated study period included all participants in the safety analysis set of period 1 that received 1 of the 3 TV-44749 treatments groups and all randomized participants to Period 2 who received at least 1 dose of TV-44749. Participants were included in their randomized treatment groups regardless of the actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind: Placebo | Integrated Study Period: Number of Participants With TEAEs and SAEs | Any TEAEs | 149 Participants |
| Double-blind: Placebo | Integrated Study Period: Number of Participants With TEAEs and SAEs | SAEs | 15 Participants |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Number of Participants With TEAEs and SAEs | Any TEAEs | 147 Participants |
| Double-blind: TV-44749 318 mg | Integrated Study Period: Number of Participants With TEAEs and SAEs | SAEs | 8 Participants |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Number of Participants With TEAEs and SAEs | Any TEAEs | 153 Participants |
| Double-blind: TV-44749 425 mg | Integrated Study Period: Number of Participants With TEAEs and SAEs | SAEs | 13 Participants |