Clinical trial NCT05693935: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-23
Enrollment: 675
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline to week 8 in the Positive and Negative Syndrome Scale (PANSS) total score
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Change in Clinical Global Impression-Severity (CGI-S) scale score from baseline to week 8
timeFrame: Baseline, Week 8
measure: Change in Personal and Social Performance Scale (PSP) score from baseline to week 8
timeFrame: Baseline, Week 8
measure: Number of participants reporting at least one Adverse Event
timeFrame: Baseline to Week 8
measure: Number of participants reporting at least one Adverse Event
timeFrame: Week 8 to Week 60
measure: Change in total PANSS score from baseline to weeks 1, 2, and 4
timeFrame: Baseline, Week 1, Week 2, Week 4
measure: Change in Clinical Global Impression-Improvement (CGI-I) scale score from baseline to weeks 4 and 8
timeFrame: Baseline, Week 4, Week 8
measure: Change in CGI-S scale score from baseline to weeks 1, 2, and 4
timeFrame: Baseline, Week 1, Week 2, Week 4
measure: Change in Patient Global Impression-Improvement (PGI-I) scale score from baseline to week 8
timeFrame: Baseline, Week 8
measure: Change in PGI-I scale score from baseline to weeks 2 and 4
timeFrame: Baseline, Week 2, Week 4
measure: Change in Schizophrenia Quality of Life Scale (SQLS) score from baseline to weeks 4 and 8
timeFrame: Baseline, Week 4, Week 8
measure: Change in PSP score from baseline to week 4
timeFrame: Baseline, Week 4
measure: Number of participants reporting use of at least one Concomitant Medication
timeFrame: Baseline to Week 8
measure: Number of participants reporting use of at least one Concomitant Medication
timeFrame: Week 8 to Week 60
measure: Number of participants that discontinued the trial
timeFrame: Baseline to Week 8
measure: Number of participants that discontinued the trial
timeFrame: Week 8 to Week 60
measure: Number of participants who Discontinued the trial due to Adverse Events
timeFrame: Baseline to Week 8
measure: Number of participants who Discontinued the trial due to Adverse Events
timeFrame: Week 8 to Week 60
measure: Change from Baseline in Abnormal Involuntary Movement Scale (AIMS) total score
timeFrame: Baseline to Week 8
measure: Change from Baseline in total score in Abnormal Involuntary Movement Scale (AIMS)
timeFrame: Week 8 to Week 60
measure: Change from baseline in Simpson-Angus Scale (SAS) mean score
timeFrame: Baseline to Week 8
measure: Change from baseline in Simpson-Angus Scale (SAS) mean score
timeFrame: Week 8 to Week 60
measure: Change from baseline in Barnes Akathisia Rating Scale (BARS) total score
timeFrame: Baseline to Week 8
measure: Change from baseline in Barnes Akathisia Rating Scale (BARS) total score
timeFrame: Week 8 to Week 60
measure: Number of participants with any suicidal ideation or suicidal behavior according to the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline to Week 8
measure: Number of participants with any suicidal ideation or suicidal behavior according to the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Week 8 to Week 60
measure: Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: Baseline to Week 8
measure: Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: Week 8 to Week 60
Other outcomes:
Locations:
city: Bentonville
country: United States
facility: Teva Investigational Site 15460
state: Arkansas
city: Little Rock
country: United States
facility: Teva Investigational Site 15465
state: Arkansas
city: Rogers
country: United States
facility: Teva Investigational Site 15453
state: Arkansas
city: Anaheim
country: United States
facility: Teva Investigational Site 15470
state: California
city: Bellflower
country: United States
facility: Teva Investigational Site 15459
state: California
city: Garden Grove
country: United States
facility: Teva Investigational Site 15490
state: California
city: La Habra
country: United States
facility: Teva Investigational Site 15474
state: California
city: Lemon Grove
country: United States
facility: Teva Investigational Site 15481
state: California
city: Long Beach
country: United States
facility: Teva Investigational Site 15491
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 15497
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 15482
state: California
city: Orange
country: United States
facility: Teva Investigational Site 15450
state: California
city: Pico Rivera
country: United States
facility: Teva Investigational Site 15455
state: California
city: Riverside
country: United States
facility: Teva Investigational Site 15471
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 15444
state: California
city: Santee
country: United States
facility: Teva Investigational Site 15449
state: California
city: Sherman Oaks
country: United States
facility: Teva Investigational Site 15461
state: California
city: Torrance
country: United States
facility: Teva Investigational Site 15483
state: California
city: Hialeah
country: United States
facility: Teva Investigational Site 15457
state: Florida
city: Hollywood
country: United States
facility: Teva Investigational Site 15488
state: Florida
city: Hollywood
country: United States
facility: Teva Investigational Site 15498
state: Florida
city: Hollywood
country: United States
facility: Teva Investigational Site 15458
state: Florida
city: Homestead
country: United States
facility: Teva Investigational Site 15489
state: Florida
city: Miami Lakes
country: United States
facility: Teva Investigational Site 15494
state: Florida
city: Miami Lakes
country: United States
facility: Teva Investigational Site 15467
state: Florida
city: Miami Lakes
country: United States
facility: Teva Investigational Site 15473
state: Florida
city: Miami Springs
country: United States
facility: Teva Investigational Site 15484
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 15452
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 15495
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 15446
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 15456
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 15479
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 15462
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 15496
state: Florida
city: West Palm Beach
country: United States
facility: Teva Investigational Site 15477
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 15468
state: Georgia
city: Decatur
country: United States
facility: Teva Investigational Site 15469
state: Georgia
city: Peachtree Corners
country: United States
facility: Teva Investigational Site 15500
state: Georgia
city: Chicago
country: United States
facility: Teva Investigational Site 15485
state: Illinois
city: Chicago
country: United States
facility: Teva Investigational Site 15480
state: Illinois
city: Shreveport
country: United States
facility: Teva Investigational Site 15447
state: Louisiana
city: Gaithersburg
country: United States
facility: Teva Investigational Site 15442
state: Maryland
city: Flowood
country: United States
facility: Teva Investigational Site 15466
state: Mississippi
city: Saint Louis
country: United States
facility: Teva Investigational Site 15487
state: Missouri
city: Marlton
country: United States
facility: Teva Investigational Site 15451
state: New Jersey
city: Charlotte
country: United States
facility: Teva Investigational Site 15441
state: North Carolina
city: Dayton
country: United States
facility: Teva Investigational Site 15454
state: Ohio
city: North Canton
country: United States
facility: Teva Investigational Site 15472
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 15478
state: Oklahoma
city: Austin
country: United States
facility: Teva Investigational Site 15448
state: Texas
city: DeSoto
country: United States
facility: Teva Investigational Site 15486
state: Texas
city: Irving
country: United States
facility: Teva Investigational Site 15464
state: Texas
city: Richardson
country: United States
facility: Teva Investigational Site 15443
state: Texas
city: Bourgas
country: Bulgaria
facility: Teva Investigational Site 59210
city: Kazanlak
country: Bulgaria
facility: Teva Investigational Site 59203
city: Lovech
country: Bulgaria
facility: Teva Investigational Site 59208
city: Pleven
country: Bulgaria
facility: Teva Investigational Site 59214
city: Plovdiv
country: Bulgaria
facility: Teva Investigational Site 59207
city: Razgrad
country: Bulgaria
facility: Teva Investigational Site 59215
city: Rousse
country: Bulgaria
facility: Teva Investigational Site 59202
city: Sliven
country: Bulgaria
facility: Teva Investigational Site 59211
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59205
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59212
city: Veliko Tarnovo
country: Bulgaria
facility: Teva Investigational Site 59209
city: Vratsa
country: Bulgaria
facility: Teva Investigational Site 59206
city: Beijing
country: China
facility: Teva Investigational Site 88052
city: Hangzhou Shi
country: China
facility: Teva Investigational Site 88044
city: Hefei
country: China
facility: Teva Investigational Site 88060
city: Jining Shi
country: China
facility: Teva Investigational Site 88055
city: Nanchang Shi
country: China
facility: Teva Investigational Site 88068
city: Shanghai
country: China
facility: Teva Investigational Site 88053
city: Tianjin
country: China
facility: Teva Investigational Site 88054
city: Wuhan
country: China
facility: Teva Investigational Site 88071
city: Xinxiang
country: China
facility: Teva Investigational Site 88072
city: Zhumadian
country: China
facility: Teva Investigational Site 88064
city: Bucuresti
country: Romania
facility: Teva Investigational Site 52124
city: Bucuresti
country: Romania
facility: Teva Investigational Site 52127
city: Iasi
country: Romania
facility: Teva Investigational Site 52123
city: Iasi
country: Romania
facility: Teva Investigational Site 52126
city: Adapazari
country: Turkey
facility: Teva Investigational Site 82058
city: Ankara
country: Turkey
facility: Teva Investigational Site 82059
city: Bursa
country: Turkey
facility: Teva Investigational Site 82057
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: