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

NCT05693935 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: TV44749-CNS-300962022-001865-11
• Study Type: interventional
• Target: 675
• Locations: 5 countries
• Sites: 82

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (22)

• Double-blind Period: Change in Clinical Global Impression-Severity (CGI-S) Scale Score From Baseline to Week 8

  Baseline, Week 8

• Double-blind Period: Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 8

  Baseline, Week 8

• Double-blind Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to Week 8

• Integrated Study Period: Number of Participants With AEs and SAEs

  Baseline up to Week 60

• Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4

  Baseline, Weeks 1, 2, and 4

Study Arms (7)

Double-blind Period: Placebo

PLACEBO COMPARATOR

Participants will receive placebo matched to TV-44749 subcutaneously (SC) once monthly over 8 weeks in double-blind period.

Drug: Placebo

Double-blind Period: TV-44749 318 mg

EXPERIMENTAL

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

Double-blind Period: TV-44749 425 mg

EXPERIMENTAL

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

Double-blind Period: TV-44749 531 mg

EXPERIMENTAL

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

Open-label Period: Placebo to TV-44749 318 mg

EXPERIMENTAL

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

Open-label Period: Placebo to TV-44749 425 mg

EXPERIMENTAL

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

Open-label Period: Placebo to TV-44749 531 mg

EXPERIMENTAL

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

Interventions

TV-44749 DRUG

In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections

Also known as: Olanzapine for Extended-Release Injectable Suspension

Double-blind Period: TV-44749 318 mg; Double-blind Period: TV-44749 425 mg; Double-blind Period: TV-44749 531 mg; Open-label Period: Placebo to TV-44749 318 mg; Open-label Period: Placebo to TV-44749 425 mg; Open-label Period: Placebo to TV-44749 531 mg

Placebo DRUG

In Period 1, 2 monthly injections (Period 1 only)

Double-blind Period: Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D LLC: lead

Study Sites (82)

Teva Investigational Site 15460

Bentonville, Arkansas, 72712, United States

Location

Teva Investigational Site 15465

Little Rock, Arkansas, 72211, United States

Location

Teva Investigational Site 15453

Rogers, Arkansas, 72758, United States

Location

Teva Investigational Site 15470

Anaheim, California, 92805, United States

Location

Teva Investigational Site 15459

Bellflower, California, 90706, United States

Location

Teva Investigational Site 15490

Garden Grove, California, 92845, United States

Location

Teva Investigational Site 15474

La Habra, California, 90631, United States

Location

Teva Investigational Site 15481

Lemon Grove, California, 91945, United States

Location

Teva Investigational Site 15491

Long Beach, California, 90807, United States

Location

Teva Investigational Site 15497

Los Angeles, California, 90015, United States

Location

Teva Investigational Site 15482

Los Angeles, California, 91436, United States

Location

Teva Investigational Site 15450

Orange, California, 92868, United States

Location

Teva Investigational Site 15455

Pico Rivera, California, 90660, United States

Location

Teva Investigational Site 15471

Riverside, California, 92506, United States

Location

Teva Investigational Site 15444

San Diego, California, 92123, United States

Location

Teva Investigational Site 15449

Santee, California, 92071, United States

Location

Teva Investigational Site 15461

Sherman Oaks, California, 91403, United States

Location

Teva Investigational Site 15483

Torrance, California, 90504, United States

Location

Teva Investigational Site 15457

Hialeah, Florida, 33016, United States

Location

Teva Investigational Site 15488

Hollywood, Florida, 33021, United States

Location

Teva Investigational Site 15498

Hollywood, Florida, 33021, United States

Location

Teva Investigational Site 15458

Hollywood, Florida, 33024, United States

Location

Teva Investigational Site 15489

Homestead, Florida, 33030, United States

Location

Teva Investigational Site 15452

Miami, Florida, 33122, United States

Location

Teva Investigational Site 15495

Miami, Florida, 33122, United States

Location

Teva Investigational Site 15446

Miami, Florida, 33155, United States

Location

Teva Investigational Site 15456

Miami, Florida, 33155, United States

Location

Teva Investigational Site 15479

Miami, Florida, 33155, United States

Location

Teva Investigational Site 15462

Miami, Florida, 33173, United States

Location

Teva Investigational Site 15496

Miami, Florida, 33176-2302, United States

Location

Teva Investigational Site 15494

Miami Lakes, Florida, 33014, United States

Location

Teva Investigational Site 15467

Miami Lakes, Florida, 33016, United States

Location

Teva Investigational Site 15473

Miami Lakes, Florida, 33016, United States

Location

Teva Investigational Site 15484

Miami Springs, Florida, 33166, United States

Location

Teva Investigational Site 15477

West Palm Beach, Florida, 33407, United States

Location

Teva Investigational Site 15468

Atlanta, Georgia, 30331, United States

Location

Teva Investigational Site 15469

Decatur, Georgia, 30030, United States

Location

Teva Investigational Site 15500

Peachtree Corners, Georgia, 30071, United States

Location

Teva Investigational Site 15485

Chicago, Illinois, 60640, United States

Location

Teva Investigational Site 15480

Chicago, Illinois, 60641, United States

Location

Teva Investigational Site 15447

Shreveport, Louisiana, 71101, United States

Location

Teva Investigational Site 15442

Gaithersburg, Maryland, 20877, United States

Location

Teva Investigational Site 15466

Flowood, Mississippi, 39232, United States

Location

Teva Investigational Site 15487

St Louis, Missouri, 63141, United States

Location

Teva Investigational Site 15451

Marlton, New Jersey, 08053, United States

Location

Teva Investigational Site 15441

Charlotte, North Carolina, 28211, United States

Location

Teva Investigational Site 15454

Dayton, Ohio, 45417, United States

Location

Teva Investigational Site 15472

North Canton, Ohio, 44720, United States

Location

Teva Investigational Site 15478

Oklahoma City, Oklahoma, 73112, United States

Location

Teva Investigational Site 15448

Austin, Texas, 78754, United States

Location

Teva Investigational Site 15486

DeSoto, Texas, 75115, United States

Location

Teva Investigational Site 15464

Irving, Texas, 75062, United States

Location

Teva Investigational Site 15443

Richardson, Texas, 75080, United States

Location

Teva Investigational Site 59210

Burgas, 8000, Bulgaria

Location

Teva Investigational Site 59203

Kazanlak, 6100, Bulgaria

Location

Teva Investigational Site 59208

Lovech, 5500, Bulgaria

Location

Teva Investigational Site 59214

Pleven, 5800, Bulgaria

Location

Teva Investigational Site 59207

Plovdiv, 4000, Bulgaria

Location

Teva Investigational Site 59215

Razgrad, 7200, Bulgaria

Location

Teva Investigational Site 59202

Rousse, 7003, Bulgaria

Location

Teva Investigational Site 59211

Sliven, 8800, Bulgaria

Location

Teva Investigational Site 59205

Sofia, 1202, Bulgaria

Location

Teva Investigational Site 59212

Sofia, 1377, Bulgaria

Location

Teva Investigational Site 59209

Veliko Tarnovo, 5000, Bulgaria

Location

Teva Investigational Site 59206

Vratsa, 3000, Bulgaria

Location

Teva Investigational Site 88052

Beijing, 100088, China

Location

Teva Investigational Site 88044

Hangzhou, 310012, China

Location

Teva Investigational Site 88060

Hefei, 230022, China

Location

Teva Investigational Site 88055

Jining Shi, 272051, China

Location

Teva Investigational Site 88068

Nanchang, 330046, China

Location

Teva Investigational Site 88053

Shanghai, 200030, China

Location

Teva Investigational Site 88054

Tianjin, 300222, China

Location

Teva Investigational Site 88071

Wuhan, 430030, China

Location

Teva Investigational Site 88072

Xinxiang, 453003, China

Location

Teva Investigational Site 88064

Zhumadian, 463002, China

Location

Teva Investigational Site 52124

Bucharest, 041914, Romania

Location

Teva Investigational Site 52127

Bucharest, 10825, Romania

Location

Teva Investigational Site 52123

Iași, 700282, Romania

Location

Teva Investigational Site 52126

Iași, 700282, Romania

Location

Teva Investigational Site 82058

Adapazarı, 54290, Turkey (Türkiye)

Location

Teva Investigational Site 82059

Ankara, 6010, Turkey (Türkiye)

Location

Teva Investigational Site 82057

Bursa, 16059, Turkey (Türkiye)

Location

Related Publications (2)

• 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.

  PMID: 41632432 DERIVED

• 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.

  PMID: 41496255 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D LLC

USMedInfo@tevapharm.com

888-483-8279

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2023
• First Posted: January 23, 2023
• Study Start: January 24, 2023
• Primary Completion: March 19, 2024
• Study Completion: January 27, 2025
• Last Updated: March 17, 2026
• Results First Posted: January 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (53); RO (4); TU (3); BU (12); CN (10)