Study 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.

Condition or Disease	Intervention/Treatment
Schizophrenia	Drug: TV-44749 - Dose level 1 Drug: TV-44749 - Dose level 2 Drug: TV-44749 - Dose level 3 Drug: Placebo

Study Design

Study Type	Interventional
Actual Enrollment	675 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Official Title	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
Study Start Date	January 24, 2023
Actual Primary Completion Date	March 19, 2024
Anticipated Study Completion Date	January 13, 2025

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
TV-44749 - Dose level 1 Low dose regimen	Drug: TV-44749 - Dose level 1 In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections
TV-44749 - Dose level 2 Medium dose regimen	Drug: TV-44749 - Dose level 2
TV-44749 - Dose level 3 High dose regimen	Drug: TV-44749 - Dose level 3
Placebo Matching Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Change from baseline to week 8 in the Positive and Negative Syndrome Scale (PANSS) total score [Baseline, Week 8]
   Data gathered from this assessment procedure are applied to the PANSS ratings. Each of the 30 items is accompanied by a specific definition as well as detailed anchoring criteria for all seven rating points. These seven points represent increasing levels of psychopathology, as follows: 1- absent 2- minimal 3- mild 4- moderate 5- moderate severe 6- severe 7- extreme.

Secondary Outcome Measures

1. Change in Clinical Global Impression-Severity (CGI-S) scale score from baseline to week 8 [Baseline, Week 8]
   The CGI-S rates this severity of a 1-7 scale, with (1) representing normal symptoms, meaning the participant is not ill. The highest on the scale, (7), represents participants among the most severely ill. Right in the middle at (4), a participant will be defined as moderately ill.
2. Change in Personal and Social Performance Scale (PSP) score from baseline to week 8 [Baseline, Week 8]
   The PSP is a clinician-based rating instrument providing an overall rating of personal and social functioning in psychiatric participants on a scale of 0 (grossly impaired functioning) to 100 (excellent functioning).
3. Number of participants reporting at least one Adverse Event [Baseline to Week 8]
   Adverse events (including serious adverse events, extrapyramidal symptoms, injection pain and other injection site reactions), vital signs (blood pressure, pulse and orthostatic changes, and temperature), body weight, lab tests and ECGs.
4. Number of participants reporting at least one Adverse Event [Week 8 to Week 60]
   Adverse events (including serious adverse events, extrapyramidal symptoms, injection pain and other injection site reactions), vital signs (blood pressure, pulse and orthostatic changes, and temperature), body weight, lab tests and ECGs.
5. Change in total PANSS score from baseline to weeks 1, 2, and 4 [Baseline, Week 1, Week 2, Week 4]
6. Change in Clinical Global Impression-Improvement (CGI-I) scale score from baseline to weeks 4 and 8 [Baseline, Week 4, Week 8]
   CGI-I scores range from 1 to 7: 0=not assessed (missing), 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse.
7. Change in CGI-S scale score from baseline to weeks 1, 2, and 4 [Baseline, Week 1, Week 2, Week 4]
8. Change in Patient Global Impression-Improvement (PGI-I) scale score from baseline to week 8 [Baseline, Week 8]
   The PGI-I score ranges from 1 (Very much better) through to 7 (Very much worse). The lower the score, the better the improvement.
9. Change in PGI-I scale score from baseline to weeks 2 and 4 [Baseline, Week 2, Week 4]
10. Change in Schizophrenia Quality of Life Scale (SQLS) score from baseline to weeks 4 and 8 [Baseline, Week 4, Week 8]
    The SQLS questionnaire assesses schizophrenia quality of life. A higher score indicates worse quality of life.
11. Change in PSP score from baseline to week 4 [Baseline, Week 4]
12. Number of participants reporting use of at least one Concomitant Medication [Baseline to Week 8]
13. Number of participants reporting use of at least one Concomitant Medication [Week 8 to Week 60]
14. Number of participants that discontinued the trial [Baseline to Week 8]
15. Number of participants that discontinued the trial [Week 8 to Week 60]
16. Number of participants who Discontinued the trial due to Adverse Events [Baseline to Week 8]
17. Number of participants who Discontinued the trial due to Adverse Events [Week 8 to Week 60]
18. Change from Baseline in Abnormal Involuntary Movement Scale (AIMS) total score [Baseline to Week 8]
19. Change from Baseline in total score in Abnormal Involuntary Movement Scale (AIMS) [Week 8 to Week 60]
20. Change from baseline in Simpson-Angus Scale (SAS) mean score [Baseline to Week 8]
21. Change from baseline in Simpson-Angus Scale (SAS) mean score [Week 8 to Week 60]
22. Change from baseline in Barnes Akathisia Rating Scale (BARS) total score [Baseline to Week 8]
23. Change from baseline in Barnes Akathisia Rating Scale (BARS) total score [Week 8 to Week 60]
24. Number of participants with any suicidal ideation or suicidal behavior according to the Columbia Suicide Severity Rating Scale (C-SSRS) [Baseline to Week 8]
25. Number of participants with any suicidal ideation or suicidal behavior according to the Columbia Suicide Severity Rating Scale (C-SSRS) [Week 8 to Week 60]
26. Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS) [Baseline to Week 8]
27. Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS) [Week 8 to Week 60]

Eligibility Criteria

Ages Eligible for Study	18 Years to 64 Years (Adult)
Sexes Eligible for Study	All
Accepts 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

Contacts and Locations

Sponsors and Collaborators	Teva Branded Pharmaceutical Products R&D, Inc.
Locations	Teva Investigational Site 15460 | Bentonville, Arkansas, United States, 72712 Teva Investigational Site 15465 | Little Rock, Arkansas, United States, 72211 Teva Investigational Site 15453 | Rogers, Arkansas, United States, 72758 Teva Investigational Site 15470 | Anaheim, California, United States, 92805 Teva Investigational Site 15459 | Bellflower, California, United States, 90706 Teva Investigational Site 15490 | Garden Grove, California, United States, 92845 Teva Investigational Site 15474 | La Habra, California, United States, 90631 Teva Investigational Site 15481 | Lemon Grove, California, United States, 91945 Teva Investigational Site 15491 | Long Beach, California, United States, 90807 Teva Investigational Site 15497 | Los Angeles, California, United States, 90015 Teva Investigational Site 15482 | Los Angeles, California, United States, 91436 Teva Investigational Site 15450 | Orange, California, United States, 92868 Teva Investigational Site 15455 | Pico Rivera, California, United States, 90660 Teva Investigational Site 15471 | Riverside, California, United States, 92506 Teva Investigational Site 15444 | San Diego, California, United States, 92102 Teva Investigational Site 15449 | Santee, California, United States, 92071 Teva Investigational Site 15461 | Sherman Oaks, California, United States, 91403 Teva Investigational Site 15483 | Torrance, California, United States, 90504 Teva Investigational Site 15457 | Hialeah, Florida, United States, 33016 Teva Investigational Site 15488 | Hollywood, Florida, United States, 33021 Teva Investigational Site 15498 | Hollywood, Florida, United States, 33021 Teva Investigational Site 15458 | Hollywood, Florida, United States, 33024 Teva Investigational Site 15489 | Homestead, Florida, United States, 33030 Teva Investigational Site 15494 | Miami Lakes, Florida, United States, 33014 Teva Investigational Site 15467 | Miami Lakes, Florida, United States, 33016 Teva Investigational Site 15473 | Miami Lakes, Florida, United States, 33016 Teva Investigational Site 15484 | Miami Springs, Florida, United States, 33166 Teva Investigational Site 15452 | Miami, Florida, United States, 33122 Teva Investigational Site 15495 | Miami, Florida, United States, 33122 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, 33155 Teva Investigational Site 15462 | Miami, Florida, United States, 33173 Teva Investigational Site 15496 | Miami, Florida, United States, 33176-2302 Teva Investigational Site 15477 | West Palm Beach, Florida, United States, 33407 Teva Investigational Site 15468 | Atlanta, Georgia, United States, 30331 Teva Investigational Site 15469 | Decatur, Georgia, United States, 30030 Teva Investigational Site 15500 | Peachtree Corners, Georgia, United States, 30071 Teva Investigational Site 15485 | Chicago, Illinois, United States, 60640 Teva Investigational Site 15480 | Chicago, Illinois, United States, 60641 Teva Investigational Site 15447 | Shreveport, Louisiana, United States, 71101 Teva Investigational Site 15442 | Gaithersburg, Maryland, United States, 20877 Teva Investigational Site 15466 | Flowood, Mississippi, United States, 39232 Teva Investigational Site 15487 | Saint Louis, Missouri, United States, 63125 Teva Investigational Site 15451 | Marlton, New Jersey, United States, 08053 Teva Investigational Site 15441 | Charlotte, North Carolina, United States, 28211 Teva Investigational Site 15454 | Dayton, Ohio, United States, 45417 Teva Investigational Site 15472 | North Canton, Ohio, United States, 44720 Teva Investigational Site 15478 | Oklahoma City, Oklahoma, United States, 73112 Teva Investigational Site 15448 | Austin, Texas, United States, 78754 Teva Investigational Site 15486 | DeSoto, Texas, United States, 75115 Teva Investigational Site 15464 | Irving, Texas, United States, 75062 Teva Investigational Site 15443 | Richardson, Texas, United States, 75080 Teva Investigational Site 59210 | Bourgas, Bulgaria, 8000 Teva Investigational Site 59203 | Kazanlak, Bulgaria, 6100 Teva Investigational Site 59208 | Lovech, Bulgaria, 5500 Teva Investigational Site 59214 | Pleven, Bulgaria, 5800 Teva Investigational Site 59207 | Plovdiv, Bulgaria, 4000 Teva Investigational Site 59215 | Razgrad, Bulgaria, 7200 Teva Investigational Site 59202 | Rousse, Bulgaria, 7003 Teva Investigational Site 59211 | Sliven, Bulgaria, 8800 Teva Investigational Site 59205 | Sofia, Bulgaria, 1202 Teva Investigational Site 59212 | Sofia, Bulgaria, 1377 Teva Investigational Site 59209 | Veliko Tarnovo, Bulgaria, 5000 Teva Investigational Site 59206 | Vratsa, Bulgaria, 3000 Teva Investigational Site 88052 | Beijing, China, 100088 Teva Investigational Site 88044 | Hangzhou Shi, China, 310012 Teva Investigational Site 88060 | Hefei, China, 230022 Teva Investigational Site 88055 | Jining Shi, China, 272051 Teva Investigational Site 88068 | Nanchang Shi, China, 330046 Teva Investigational Site 88053 | Shanghai, China, 200030 Teva Investigational Site 88054 | Tianjin Shi, China, 300222 Teva Investigational Site 88071 | Wuhan, China, 430030 Teva Investigational Site 88072 | Xinxiang, China, 453003 Teva Investigational Site 88064 | Zhumadian, China, 463002 Teva Investigational Site 52124 | Bucuresti, Romania, 041914 Teva Investigational Site 52127 | Bucuresti, Romania, 10825 Teva Investigational Site 52123 | Iasi, Romania, 700282 Teva Investigational Site 52126 | Iasi, Romania, 700282 Teva Investigational Site 82058 | Adapazari, Turkey, 54290 Teva Investigational Site 82059 | Ankara, Turkey, 6010 Teva Investigational Site 82057 | Bursa, Turkey, 16059
Investigators

More Information

Additional Relevant MeSH Terms

• Schizophrenia
• Schizophrenia Spectrum and Other Psychotic Disorders
• Mental Disorders