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

Schizophrenia Clinical Trial

— SOLARIS  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05693935
• Other study ID #: TV44749-CNS-30096
• Secondary ID: 2022-001865-11
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 24, 2023
• Est. completion date: January 13, 2025

Study information

• Verified date: April 2024
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 675
• Est. completion date: January 13, 2025
• Est. primary completion date: March 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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 (ß-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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

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
In Period 1, 2 monthly injections, In Period 2 up to 12 monthly injections
• TV-44749 - Dose level 3
In Period 1, 2 monthly injections. In Period 2, up to 12 monthly injections
• Placebo
In Period 1, 2 monthly injections (Period 1 only)

Locations

Country	Name	City	State
Bulgaria	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
China	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 Shi
China	Teva Investigational Site 88071	Wuhan
China	Teva Investigational Site 88072	Xinxiang
China	Teva Investigational Site 88064	Zhumadian
Romania	Teva Investigational Site 52124	Bucuresti
Romania	Teva Investigational Site 52127	Bucuresti
Romania	Teva Investigational Site 52123	Iasi
Romania	Teva Investigational Site 52126	Iasi
Turkey	Teva Investigational Site 82058	Adapazari
Turkey	Teva Investigational Site 82059	Ankara
Turkey	Teva Investigational Site 82057	Bursa
United States	Teva Investigational Site 15470	Anaheim	California
United States	Teva Investigational Site 15468	Atlanta	Georgia
United States	Teva Investigational Site 15448	Austin	Texas
United States	Teva Investigational Site 15459	Bellflower	California
United States	Teva Investigational Site 15460	Bentonville	Arkansas
United States	Teva Investigational Site 15441	Charlotte	North Carolina
United States	Teva Investigational Site 15480	Chicago	Illinois
United States	Teva Investigational Site 15485	Chicago	Illinois
United States	Teva Investigational Site 15454	Dayton	Ohio
United States	Teva Investigational Site 15469	Decatur	Georgia
United States	Teva Investigational Site 15486	DeSoto	Texas
United States	Teva Investigational Site 15466	Flowood	Mississippi
United States	Teva Investigational Site 15442	Gaithersburg	Maryland
United States	Teva Investigational Site 15490	Garden Grove	California
United States	Teva Investigational Site 15457	Hialeah	Florida
United States	Teva Investigational Site 15458	Hollywood	Florida
United States	Teva Investigational Site 15488	Hollywood	Florida
United States	Teva Investigational Site 15498	Hollywood	Florida
United States	Teva Investigational Site 15489	Homestead	Florida
United States	Teva Investigational Site 15464	Irving	Texas
United States	Teva Investigational Site 15474	La Habra	California
United States	Teva Investigational Site 15481	Lemon Grove	California
United States	Teva Investigational Site 15465	Little Rock	Arkansas
United States	Teva Investigational Site 15491	Long Beach	California
United States	Teva Investigational Site 15482	Los Angeles	California
United States	Teva Investigational Site 15497	Los Angeles	California
United States	Teva Investigational Site 15451	Marlton	New Jersey
United States	Teva Investigational Site 15446	Miami	Florida
United States	Teva Investigational Site 15452	Miami	Florida
United States	Teva Investigational Site 15456	Miami	Florida
United States	Teva Investigational Site 15462	Miami	Florida
United States	Teva Investigational Site 15479	Miami	Florida
United States	Teva Investigational Site 15495	Miami	Florida
United States	Teva Investigational Site 15496	Miami	Florida
United States	Teva Investigational Site 15467	Miami Lakes	Florida
United States	Teva Investigational Site 15473	Miami Lakes	Florida
United States	Teva Investigational Site 15494	Miami Lakes	Florida
United States	Teva Investigational Site 15484	Miami Springs	Florida
United States	Teva Investigational Site 15472	North Canton	Ohio
United States	Teva Investigational Site 15478	Oklahoma City	Oklahoma
United States	Teva Investigational Site 15450	Orange	California
United States	Teva Investigational Site 15500	Peachtree Corners	Georgia
United States	Teva Investigational Site 15455	Pico Rivera	California
United States	Teva Investigational Site 15443	Richardson	Texas
United States	Teva Investigational Site 15471	Riverside	California
United States	Teva Investigational Site 15453	Rogers	Arkansas
United States	Teva Investigational Site 15487	Saint Louis	Missouri
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 15447	Shreveport	Louisiana
United States	Teva Investigational Site 15483	Torrance	California
United States	Teva Investigational Site 15477	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  China,  Romania,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to week 8 in the Positive and Negative Syndrome Scale (PANSS) total score	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.	Baseline, Week 8
Secondary	Change in Clinical Global Impression-Severity (CGI-S) scale score from baseline to 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.	Baseline, Week 8
Secondary	Change in Personal and Social Performance Scale (PSP) score from baseline to 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).	Baseline, Week 8
Secondary	Number of participants reporting at least one Adverse Event	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.	Baseline to Week 8
Secondary	Number of participants reporting at least one Adverse Event	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.	Week 8 to Week 60
Secondary	Change in total PANSS score from baseline to weeks 1, 2, and 4		Baseline, Week 1, Week 2, Week 4
Secondary	Change in Clinical Global Impression-Improvement (CGI-I) scale score from baseline to weeks 4 and 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.	Baseline, Week 4, Week 8
Secondary	Change in CGI-S scale score from baseline to weeks 1, 2, and 4		Baseline, Week 1, Week 2, Week 4
Secondary	Change in Patient Global Impression-Improvement (PGI-I) scale score from baseline to 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.	Baseline, Week 8
Secondary	Change in PGI-I scale score from baseline to weeks 2 and 4		Baseline, Week 2, Week 4
Secondary	Change in Schizophrenia Quality of Life Scale (SQLS) score from baseline to weeks 4 and 8	The SQLS questionnaire assesses schizophrenia quality of life. A higher score indicates worse quality of life.	Baseline, Week 4, Week 8
Secondary	Change in PSP score from baseline to week 4		Baseline, Week 4
Secondary	Number of participants reporting use of at least one Concomitant Medication		Baseline to Week 8
Secondary	Number of participants reporting use of at least one Concomitant Medication		Week 8 to Week 60
Secondary	Number of participants that discontinued the trial		Baseline to Week 8
Secondary	Number of participants that discontinued the trial		Week 8 to Week 60
Secondary	Number of participants who Discontinued the trial due to Adverse Events		Baseline to Week 8
Secondary	Number of participants who Discontinued the trial due to Adverse Events		Week 8 to Week 60
Secondary	Change from Baseline in Abnormal Involuntary Movement Scale (AIMS) total score		Baseline to Week 8
Secondary	Change from Baseline in total score in Abnormal Involuntary Movement Scale (AIMS)		Week 8 to Week 60
Secondary	Change from baseline in Simpson-Angus Scale (SAS) mean score		Baseline to Week 8
Secondary	Change from baseline in Simpson-Angus Scale (SAS) mean score		Week 8 to Week 60
Secondary	Change from baseline in Barnes Akathisia Rating Scale (BARS) total score		Baseline to Week 8
Secondary	Change from baseline in Barnes Akathisia Rating Scale (BARS) total score		Week 8 to Week 60
Secondary	Number of participants with any suicidal ideation or suicidal behavior according to the Columbia Suicide Severity Rating Scale (C-SSRS)		Baseline to Week 8
Secondary	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
Secondary	Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS)		Baseline to Week 8
Secondary	Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS)		Week 8 to Week 60