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

Phase 3

Active, not recruiting

• Conditions: Schizophrenia
• Interventions: Drug: TV-44749 - Dose level 3; Drug: TV-44749 - Dose level 1; Drug: Placebo; Drug: TV-44749 - Dose level 2

• Registration Number: NCT05693935
• Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

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.

Study Timeline

• Study First Submitted: 2023-01-12
• Study First Submitted QC: 2023-01-12
• Study First Posted: 2023-01-23
• Study Start: 2023-01-24
• Primary Completion: 2024-03-19
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-02
• Last Update Posted: 2025-01-03
• Study Completion: 2025-01-13

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 675

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TV-44749 - Dose level 3	TV-44749 - Dose level 3	High dose regimen
TV-44749 - Dose level 1	TV-44749 - Dose level 1	Low dose regimen
Placebo	Placebo	Matching Placebo
TV-44749 - Dose level 2	TV-44749 - Dose level 2	Medium dose regimen

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Change in CGI-S scale score from baseline to weeks 1, 2, and 4	Baseline, Week 1, Week 2, Week 4
Number of participants that discontinued the trial	Week 8 to Week 60
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.
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.
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.
Change in total PANSS score from baseline to weeks 1, 2, and 4	Baseline, Week 1, Week 2, Week 4
Change in PSP score from baseline to week 4	Baseline, Week 4
Number of participants reporting use of at least one Concomitant Medication	Week 8 to Week 60
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).
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.
Change from baseline in Simpson-Angus Scale (SAS) mean score	Week 8 to Week 60
Change from baseline in Barnes Akathisia Rating Scale (BARS) total score	Week 8 to Week 60
Number of participants who Discontinued the trial due to Adverse Events	Week 8 to Week 60
Change from Baseline in total score in Abnormal Involuntary Movement Scale (AIMS)	Week 8 to Week 60
Change in PGI-I scale score from baseline to weeks 2 and 4	Baseline, Week 2, Week 4
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.
Change from Baseline in Abnormal Involuntary Movement Scale (AIMS) total score	Baseline to Week 8
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
Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS)	Week 8 to Week 60

Trial Locations

Locations (82)

Teva Investigational Site 15460; 🇺🇸 Bentonville, Arkansas, United States

Teva Investigational Site 15465; 🇺🇸 Little Rock, Arkansas, United States

Teva Investigational Site 15453; 🇺🇸 Rogers, Arkansas, United States

Teva Investigational Site 15470; 🇺🇸 Anaheim, California, United States

Teva Investigational Site 15459; 🇺🇸 Bellflower, California, United States

Teva Investigational Site 15490; 🇺🇸 Garden Grove, California, United States

Teva Investigational Site 15474; 🇺🇸 La Habra, California, United States

Teva Investigational Site 15481; 🇺🇸 Lemon Grove, California, United States

Teva Investigational Site 15491; 🇺🇸 Long Beach, California, United States

Teva Investigational Site 15497; 🇺🇸 Los Angeles, California, United States

Teva Investigational Site 15450; 🇺🇸 Orange, California, United States

Teva Investigational Site 15482; 🇺🇸 Panorama City, California, United States

Teva Investigational Site 15455; 🇺🇸 Pico Rivera, California, United States

Teva Investigational Site 15471; 🇺🇸 Riverside, California, United States

Teva Investigational Site 15444; 🇺🇸 San Diego, California, United States

Teva Investigational Site 15449; 🇺🇸 Santee, California, United States

Teva Investigational Site 15461; 🇺🇸 Sherman Oaks, California, United States

Teva Investigational Site 15483; 🇺🇸 Torrance, California, United States

Teva Investigational Site 15457; 🇺🇸 Hialeah, Florida, United States

Teva Investigational Site 15488; 🇺🇸 Hollywood, Florida, United States

Teva Investigational Site 15498; 🇺🇸 Hollywood, Florida, United States

Teva Investigational Site 15458; 🇺🇸 Hollywood, Florida, United States

Teva Investigational Site 15489; 🇺🇸 Homestead, Florida, United States

Teva Investigational Site 15494; 🇺🇸 Miami Lakes, Florida, United States

Teva Investigational Site 15467; 🇺🇸 Miami Lakes, Florida, United States

Teva Investigational Site 15473; 🇺🇸 Miami Lakes, Florida, United States

Teva Investigational Site 15484; 🇺🇸 Miami Springs, Florida, United States

Teva Investigational Site 15452; 🇺🇸 Miami, Florida, United States

Teva Investigational Site 15495; 🇺🇸 Miami, Florida, United States

Teva Investigational Site 15446; 🇺🇸 Miami, Florida, United States

Teva Investigational Site 15456; 🇺🇸 Miami, Florida, United States

Teva Investigational Site 15479; 🇺🇸 Miami, Florida, United States

Teva Investigational Site 15462; 🇺🇸 Miami, Florida, United States

Teva Investigational Site 15496; 🇺🇸 Miami, Florida, United States

Teva Investigational Site 15477; 🇺🇸 West Palm Beach, Florida, United States

Teva Investigational Site 15468; 🇺🇸 Atlanta, Georgia, United States

Teva Investigational Site 15469; 🇺🇸 Decatur, Georgia, United States

Teva Investigational Site 15500; 🇺🇸 Peachtree Corners, Georgia, United States

Teva Investigational Site 15441; 🇺🇸 Charlotte, North Carolina, United States

Teva Investigational Site 15454; 🇺🇸 Dayton, Ohio, United States

Teva Investigational Site 15472; 🇺🇸 North Canton, Ohio, United States

Teva Investigational Site 15485; 🇺🇸 Chicago, Illinois, United States

Teva Investigational Site 15480; 🇺🇸 Chicago, Illinois, United States

Teva Investigational Site 15447; 🇺🇸 Shreveport, Louisiana, United States

Teva Investigational Site 15442; 🇺🇸 Gaithersburg, Maryland, United States

Teva Investigational Site 15466; 🇺🇸 Flowood, Mississippi, United States

Teva Investigational Site 15487; 🇺🇸 Saint Louis, Missouri, United States

Teva Investigational Site 15451; 🇺🇸 Marlton, New Jersey, United States

Teva Investigational Site 15478; 🇺🇸 Oklahoma City, Oklahoma, United States

Teva Investigational Site 15448; 🇺🇸 Austin, Texas, United States

Teva Investigational Site 15486; 🇺🇸 DeSoto, Texas, United States

Teva Investigational Site 15464; 🇺🇸 Irving, Texas, United States

Teva Investigational Site 15443; 🇺🇸 Richardson, Texas, United States

Teva Investigational Site 59210; 🇧🇬 Bourgas, Bulgaria

Teva Investigational Site 59203; 🇧🇬 Kazanlak, Bulgaria

Teva Investigational Site 59208; 🇧🇬 Lovech, Bulgaria

Teva Investigational Site 59214; 🇧🇬 Pleven, Bulgaria

Teva Investigational Site 59207; 🇧🇬 Plovdiv, Bulgaria

Teva Investigational Site 59215; 🇧🇬 Razgrad, Bulgaria

Teva Investigational Site 59202; 🇧🇬 Rousse, Bulgaria

Teva Investigational Site 59211; 🇧🇬 Sliven, Bulgaria

Teva Investigational Site 59205; 🇧🇬 Sofia, Bulgaria

Teva Investigational Site 59212; 🇧🇬 Sofia, Bulgaria

Teva Investigational Site 59209; 🇧🇬 Veliko Tarnovo, Bulgaria

Teva Investigational Site 59206; 🇧🇬 Vratsa, Bulgaria

Teva Investigational Site 88052; 🇨🇳 Beijing, China

Teva Investigational Site 88044; 🇨🇳 Hangzhou Shi, China

Teva Investigational Site 88060; 🇨🇳 Hefei, China

Teva Investigational Site 88055; 🇨🇳 Jining Shi, China

Teva Investigational Site 88068; 🇨🇳 Nanchang Shi, China

Teva Investigational Site 88053; 🇨🇳 Shanghai, China

Teva Investigational Site 88054; 🇨🇳 Tianjin, China

Teva Investigational Site 88071; 🇨🇳 Wuhan, China

Teva Investigational Site 88072; 🇨🇳 Xinxiang, China

Teva Investigational Site 88064; 🇨🇳 Zhumadian, China

Teva Investigational Site 52124; 🇷🇴 Bucuresti, Romania

Teva Investigational Site 52127; 🇷🇴 Bucuresti, Romania

Teva Investigational Site 52123; 🇷🇴 Iasi, Romania

Teva Investigational Site 82058; 🇹🇷 Adapazari, Turkey

Teva Investigational Site 52126; 🇷🇴 Iasi, Romania

Teva Investigational Site 82057; 🇹🇷 Bursa, Turkey

Teva Investigational Site 82059; 🇹🇷 Ankara, Turkey