A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label, Long-Term Safety Phase to Evaluate the Efficacy and Safety of TV-44749 in Adults With Schizophrenia (SOLARIS)

A Multinational, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study With an Open-Label, Long-Term Safety Phase to Evaluate the Efficacy, Safety, and Tolerability of Olanzapine for Extended-Release Injectable Suspension (TV-44749) for Subcutaneous Use as Treatment of Adult Patients With Schizophrenia

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: TV-44749

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.

• Study Type: Interventional
• Enrollment (Actual): 675
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Teva Investigational Site 59210
  • Kazanlak, Bulgaria, 6100
    • Teva Investigational Site 59203
  • Lovech, Bulgaria, 5500
    • Teva Investigational Site 59208
  • Pleven, Bulgaria, 5800
    • Teva Investigational Site 59214
  • Plovdiv, Bulgaria, 4000
    • Teva Investigational Site 59207
  • Razgrad, Bulgaria, 7200
    • Teva Investigational Site 59215
  • Rousse, Bulgaria, 7003
    • Teva Investigational Site 59202
  • Sliven, Bulgaria, 8800
    • Teva Investigational Site 59211
  • Sofia, Bulgaria, 1202
    • Teva Investigational Site 59205
  • Sofia, Bulgaria, 1377
    • Teva Investigational Site 59212
  • Veliko Tarnovo, Bulgaria, 5000
    • Teva Investigational Site 59209
  • Vratsa, Bulgaria, 3000
    • Teva Investigational Site 59206
• China
  • Beijing, China, 100088
    • Teva Investigational Site 88052
  • Hangzhou, China, 310012
    • Teva Investigational Site 88044
  • Hefei, China, 230022
    • Teva Investigational Site 88060
  • Jining Shi, China, 272051
    • Teva Investigational Site 88055
  • Nanchang, China, 330046
    • Teva Investigational Site 88068
  • Shanghai, China, 200030
    • Teva Investigational Site 88053
  • Tianjin, China, 300222
    • Teva Investigational Site 88054
  • Wuhan, China, 430030
    • Teva Investigational Site 88071
  • Xinxiang, China, 453003
    • Teva Investigational Site 88072
  • Zhumadian, China, 463002
    • Teva Investigational Site 88064
• Romania
  • Bucharest, Romania, 041914
    • Teva Investigational Site 52124
  • Bucharest, Romania, 10825
    • Teva Investigational Site 52127
  • Iași, Romania, 700282
    • Teva Investigational Site 52123
  • Iași, Romania, 700282
    • Teva Investigational Site 52126
• Turkey (Türkiye)
  • Adapazarı, Turkey (Türkiye), 54290
    • Teva Investigational Site 82058
  • Ankara, Turkey (Türkiye), 6010
    • Teva Investigational Site 82059
  • Bursa, Turkey (Türkiye), 16059
    • Teva Investigational Site 82057
• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Teva Investigational Site 15460
    • Little Rock, Arkansas, United States, 72211
      • Teva Investigational Site 15465
    • Rogers, Arkansas, United States, 72758
      • Teva Investigational Site 15453
  • California
    • Anaheim, California, United States, 92805
      • Teva Investigational Site 15470
    • Bellflower, California, United States, 90706
      • Teva Investigational Site 15459
    • Garden Grove, California, United States, 92845
      • Teva Investigational Site 15490
    • La Habra, California, United States, 90631
      • Teva Investigational Site 15474
    • Lemon Grove, California, United States, 91945
      • Teva Investigational Site 15481
    • Long Beach, California, United States, 90807
      • Teva Investigational Site 15491
    • Los Angeles, California, United States, 90015
      • Teva Investigational Site 15497
    • Los Angeles, California, United States, 91436
      • Teva Investigational Site 15482
    • Orange, California, United States, 92868
      • Teva Investigational Site 15450
    • Pico Rivera, California, United States, 90660
      • Teva Investigational Site 15455
    • Riverside, California, United States, 92506
      • Teva Investigational Site 15471
    • San Diego, California, United States, 92123
      • Teva Investigational Site 15444
    • Santee, California, United States, 92071
      • Teva Investigational Site 15449
    • Sherman Oaks, California, United States, 91403
      • Teva Investigational Site 15461
    • Torrance, California, United States, 90504
      • Teva Investigational Site 15483
  • Florida
    • Hialeah, Florida, United States, 33016
      • Teva Investigational Site 15457
    • Hollywood, Florida, United States, 33021
      • Teva Investigational Site 15488
    • Hollywood, Florida, United States, 33021
      • Teva Investigational Site 15498
    • Hollywood, Florida, United States, 33024
      • Teva Investigational Site 15458
    • Homestead, Florida, United States, 33030
      • Teva Investigational Site 15489
    • Miami, Florida, United States, 33122
      • Teva Investigational Site 15452
    • Miami, Florida, United States, 33122
      • Teva Investigational Site 15495
    • Miami, Florida, United States, 33155
      • Teva Investigational Site 15446
    • Miami, Florida, United States, 33155
      • Teva Investigational Site 15456
    • Miami, Florida, United States, 33155
      • Teva Investigational Site 15479
    • Miami, Florida, United States, 33173
      • Teva Investigational Site 15462
    • Miami, Florida, United States, 33176-2302
      • Teva Investigational Site 15496
    • Miami Lakes, Florida, United States, 33014
      • Teva Investigational Site 15494
    • Miami Lakes, Florida, United States, 33016
      • Teva Investigational Site 15467
    • Miami Lakes, Florida, United States, 33016
      • Teva Investigational Site 15473
    • Miami Springs, Florida, United States, 33166
      • Teva Investigational Site 15484
    • West Palm Beach, Florida, United States, 33407
      • Teva Investigational Site 15477
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Teva Investigational Site 15468
    • Decatur, Georgia, United States, 30030
      • Teva Investigational Site 15469
    • Peachtree Corners, Georgia, United States, 30071
      • Teva Investigational Site 15500
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Teva Investigational Site 15485
    • Chicago, Illinois, United States, 60641
      • Teva Investigational Site 15480
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Teva Investigational Site 15447
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • Teva Investigational Site 15442
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Teva Investigational Site 15466
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Teva Investigational Site 15487
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Teva Investigational Site 15451
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Teva Investigational Site 15441
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Teva Investigational Site 15454
    • North Canton, Ohio, United States, 44720
      • Teva Investigational Site 15472
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Teva Investigational Site 15478
  • Texas
    • Austin, Texas, United States, 78754
      • Teva Investigational Site 15448
    • DeSoto, Texas, United States, 75115
      • Teva Investigational Site 15486
    • Irving, Texas, United States, 75062
      • Teva Investigational Site 15464
    • Richardson, Texas, United States, 75080
      • Teva Investigational Site 15443

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Double-blind Period: Placebo; Participants will receive placebo matched to TV-44749 subcutaneously (SC) once monthly over 8 weeks in double-blind period.	Drug: Placebo; In Period 1, 2 monthly injections (Period 1 only)
Experimental: Double-blind Period: TV-44749 318 mg; Participants will receive TV-44749 extended-release injectable suspension at a dose of 318 milligrams (mg) SC once monthly over 8 weeks in double-blind period.	Drug: TV-44749; In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections; Other Names: Olanzapine for Extended-Release Injectable Suspension
Experimental: Double-blind Period: TV-44749 425 mg; Participants will receive TV-44749 extended-release injectable suspension at a dose of 425 mg SC once monthly over 8 weeks in double-blind period.	Drug: TV-44749; In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections; Other Names: Olanzapine for Extended-Release Injectable Suspension
Experimental: Double-blind Period: TV-44749 531 mg; Participants will receive TV-44749 extended-release injectable suspension at a dose of 531 mg SC once monthly over 8 weeks in double-blind period.	Drug: TV-44749; In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections; Other Names: Olanzapine for Extended-Release Injectable Suspension
Experimental: Open-label Period: Placebo to TV-44749 318 mg; Participants who receive placebo during the double-blind period, will receive TV-44749 extended-release injectable suspension at a dose of 318 mg SC once monthly for up to 48 weeks in open-label period.	Drug: TV-44749; In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections; Other Names: Olanzapine for Extended-Release Injectable Suspension
Experimental: Open-label Period: Placebo to TV-44749 425 mg; Participants who receive placebo during the double-blind period, will receive TV-44749 extended-release injectable suspension at a dose of 425 mg SC once monthly for up to 48 weeks in open-label period.	Drug: TV-44749; In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections; Other Names: Olanzapine for Extended-Release Injectable Suspension
Experimental: Open-label Period: Placebo to TV-44749 531 mg; Participants who receive placebo during the double-blind period, will receive TV-44749 extended-release injectable suspension at a dose of 531 mg SC once monthly for up to 48 weeks in open-label period.	Drug: TV-44749; In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections; Other Names: Olanzapine for Extended-Release Injectable Suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 8
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.	Baseline, Week 8
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.	Baseline, Weeks 1, 2, and 4
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.	Weeks 4 and 8
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.	Baseline, Weeks 1, 2, and 4
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.	Weeks 2, 4, and 8
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.	Baseline, Weeks 4 and 8
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.	Baseline, Week 4
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.	Baseline up to Week 8
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.	Baseline up to Week 60
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.	Baseline, Week 8
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.	Baseline, Week 8
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.	Baseline, Week 8
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.	Baseline up to Week 8
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.	Baseline up to Week 60
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.	Baseline, Week 8
Double-blind Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (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 summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section.	Baseline up to Week 8
Integrated Study Period: Number of Participants With AEs 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 summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section.	Baseline up to Week 60
Integrated Study Period: Change From Baseline to Week 60 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.	Baseline, Week 60
Integrated Study Period: Change From Baseline to Week 60 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.	Baseline, Week 60
Integrated Study Period: Change From Baseline to Week 60 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.	Baseline, Week 60
Integrated Study Period: Change From Baseline to Week 60 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.	Baseline, Week 60

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D LLC
• Investigators: Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D LLC

Publications and helpful links

General Publications

• Perlstein I, Cherniakov I, Elgart A, Gomeni R, Gutman D, Merenlender Wagner A, Singh R. Population Pharmacokinetic Model-Based Dose Selection of Extended-Release Injectable Olanzapine (TV-44749) for Subcutaneous Use in Phase 3 Clinical Trial in Adults with Schizophrenia. J Clin Pharmacol. 2026 Jan;66(1):e70144. doi: 10.1002/jcph.70144.
• Cherniakov I, Wagner AM, Eshet R, Tiver R, Bibi D, Perlstein I, Kalmanczhelyi A, Sharon N, Cohen G, Ferderber K, Roberts J, Elgart A, Gutman D, Rabinovich-Guilatt L. Safety, Tolerability, and Pharmacokinetics of Subcutaneous Extended-Release Injectable Olanzapine in Patients with Schizophrenia and Schizoaffective Disorder. Clin Drug Investig. 2026 Mar;46(3):307-320. doi: 10.1007/s40261-025-01507-x. Epub 2026 Feb 3.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2023
• Primary Completion (Actual): March 19, 2024
• Study Completion (Actual): January 27, 2025

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: January 12, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Olanzapine
• Other Study ID Numbers: TV44749-CNS-30096; 2022-001865-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be assessed for scientific merit, product approval status, and conflicts of interest. If the request is approved, patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No