A Study to Test if TV-46000 is Safe for Maintenance Treatment of Schizophrenia

Schizophrenia Clinical Trial

— SHINE  

Official title:

A Study to Evaluate the Safety, Tolerability, and Effect of Risperidone Extended-Release Injectable Suspension (TV-46000) for Subcutaneous Use as Maintenance Treatment in Adult and Adolescent Patients With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03893825
• Other study ID #: TV46000-CNS-30078
• Secondary ID: 2019-000063-24
• Status: Completed
• Phase: Phase 3
• Start date: April 17, 2019
• Est. completion date: December 2, 2021

Study information

• Verified date: December 2022
• 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 the study is to evaluate the long-term safety and tolerability of TV-46000. The primary safety and tolerability endpoint is the frequency of all adverse events, including serious adverse events. For new participants, the total duration of participant participation in the study is planned to be up to 80 weeks (including a screening period of up to 4 weeks, a 12-week oral conversion/stabilization stage [Stage 1], a 56-week double-blind maintenance stage [Stage 2], and a follow-up period [8 weeks]). For roll-over participants, the total duration of participant participation in the study is planned to be up to 64 weeks (including up to 56 weeks in the maintenance stage [Stage 2] and a follow-up period [8 weeks]). Participants who started Stage 2 who relapse or meet 1 or more of the withdrawal criteria should be invited to perform the Early Termination visit as soon as possible within 4 weeks of the last injection. Participants who withdraw from the study before completing the 56-week maintenance stage will have follow-up procedures and assessments performed at their follow-up visits. During the follow-up period, participants will be treated according to the investigator's judgment. All participants will be treated with active drug.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 336
• Est. completion date: December 2, 2021
• Est. primary completion date: December 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 65 Years

Eligibility

Inclusion Criteria:

Participants Rolling Over from the Pivotal Efficacy Study TV46000-CNS-30072:

• The participant must have participated in the pivotal efficacy study (Study TV46000-CNS-30072) without experiencing relapse events and without important protocol deviations.
• If the participant was taking antidepressants or mood stabilizers in Study TV46000-CNS-30072, no dose changes or initiation of treatment with these medications will be permitted.
• The participant, in the investigator's judgment, requires chronic treatment with an antipsychotic medication.
• The participant is able to understand the nature of the study and follow protocol requirements, including the prescribed dosage regimens (oral and SC administration) and non-use of prohibited concomitant medications; can read and understand the written word in order to complete participant-reported outcomes measures; and can be reliably rated on assessment scales.
• The participant has had a stable place of residence for the previous 3 months before the baseline visit in this study, and changes in residence are not anticipated over the course of study participation.
• The participant has no significant life events (such as pending loss of housing, family status change, long travel abroad, surgery, etc) that could affect study outcomes expected throughout the period of study participation.
• Women of childbearing potential and sexually active female adolescents 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 and agree to continue use of this method beginning 1 month before the first administration of study drug and for the duration of the study and for 120 days after the last injection of study drug.
• The participant, if adult or adolescent male, is surgically sterile, or, if capable of producing offspring, has exclusively same-sex partners or is currently using an approved method of birth control and agrees to the continued use of this method for the duration of the study (and for 120 days after the last dose of study drug). Male participants with sex partners who are women of childbearing potential must use condoms even if surgically sterile. In addition, male participants may not donate sperm for the duration of the study and for 120 days after taking the study drug.

New Participants (Not Rolling Over from the Pivotal Efficacy Study TV46000-CNS-30072):

• The participant has a diagnosis of schizophrenia
• The participant has been responsive to an antipsychotic treatment (other than clozapine) in the past year based on investigator judgment (and discussions with family members, caregivers, or healthcare professionals as applicable).
• The participant, in the investigator's judgment, requires chronic treatment with an antipsychotic medication.
• The participant is able to understand the nature of the study and follow protocol requirements, including the prescribed dosage regimens (oral and sc administration) and non-use of prohibited concomitant medications; can read and understand the written word in order to complete participant-reported outcomes measures; and can be reliably rated on assessment scales.
• The participant has had a stable place of residence for the previous 3 months before screening, and changes in residence are not anticipated over the course of study participation.
• The participant has no significant life events (such as pending loss of housing, family status change, long travel abroad, surgery, etc) that could affect study outcomes expected throughout the period of study participation.
• The participant has a body mass index between 18.0 and 38.0 kilograms (kg)/square meter (m^2), inclusive.
• Women of childbearing potential and sexually active female adolescents 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 and agree to continue use of this method beginning 1 month before the first administration of study drug and for the duration of the study and for 120 days after the last injection of study drug.
• The participant, if adult or adolescent male, is surgically sterile, or, if capable of producing offspring, has exclusively same-sex partners or is currently using an approved method of birth control and agrees to the continued use of this method for the duration of the study (and for 120 days after the last dose of study drug). Male participants with sex partners who are women of childbearing potential must use condoms even if surgically sterile. In addition, male participants may not donate sperm for the duration of the study and for 120 days after taking the study drug.
• Additional criteria apply, please contact the investigator for more information. Exclusion Criteria:

Participants Rolling Over from the Pivotal Efficacy Study TV46000-CNS-30072:

• The participant has a finding in the baseline 12-lead electrocardiogram (ECG) that is considered clinically significant in the judgment of the investigator.
• Poor compliance with study procedures (in the opinion of the investigator or sponsor) during the pivotal efficacy Study TV46000-CNS-30072. This should be discussed on a case-by-case basis. New Participants (Not Rolling Over from the Pivotal Efficacy Study TV46000-CNS-30072) and

Roll-Over Participants:

• The participant is currently on clozapine or has received electroconvulsive therapy in the last 12 months.
• The participant has a history of epilepsy or seizures, neuroleptic malignant syndrome, tardive dyskinesia, or other medical condition that would expose the participant to undue risk.
• The participant has a positive serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B surface antigen, and/or hepatitis C.
• The participant has current or a history of known hypersensitivity to risperidone or any of the excipients of TV-46000 or the oral formulation of risperidone used in the stabilization phase.
• The participant has a substance use disorder, including alcohol and benzodiazepines but excluding nicotine and caffeine.
• The participant is a pregnant or lactating female.
• The participant has used an investigational drug other than TV-46000 within 3 months prior to screening or has participated in a non-drug clinical trial within 30 days prior to screening.
• Vulnerable participants (for example, people kept in detention).
• Additional criteria apply, please contact the investigator for more information.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• TV-46000
TV-46000 will be administered per dose and schedule specified in the arm description.
• Placebo
Placebo matching to TV-46000 will be administered per schedule specified in the arm description.

Locations

Country	Name	City	State
Bulgaria	Teva Investigational Site 59148	Bourgas
Bulgaria	Teva Investigational Site 59152	Kazanlak
Bulgaria	Teva Investigational Site 59151	Lovech
Bulgaria	Teva Investigational Site 59149	Novi Iskar
Bulgaria	Teva Investigational Site 59144	Sofia
Bulgaria	Teva Investigational Site 59150	Varna
Bulgaria	Teva Investigational Site 59154	Varna
Bulgaria	Teva Investigational Site 59146	Vratsa
Canada	Teva Investigational Site 11171	Calgary	AL
Canada	Teva Investigational Site 11170	Chatham	Ontario
Canada	Teva Investigational Site 11169	Edmonton	Alberta
Canada	Teva Investigational Site 11174	Montreal	Quebec
Canada	Teva Investigational Site 11173	Vancouver	British Columbia
France	Teva Investigational Site 35259	Clermont Ferrand Cedex 1
France	Teva Investigational Site 35257	Douai
France	Teva Investigational Site 35260	Nice cedex 1
France	Teva Investigational Site 35256	Toulon
Israel	Teva Investigational Site 80162	Afula
Israel	Teva Investigational Site 80161	Ashkelon
Israel	Teva Investigational Site 80156	Haifa
Israel	Teva Investigational Site 80155	Hod Hasharon
Israel	Teva Investigational Site 80157	Ramat Gan
Israel	Teva Investigational Site 80160	Tel Aviv
United States	Teva Investigational Site 14811	Anaheim	California
United States	Teva Investigational Site 14416	Beachwood	Ohio
United States	Teva Investigational Site 14395	Bellevue	Washington
United States	Teva Investigational Site 14794	Bellflower	California
United States	Teva Investigational Site 14792	Berlin	New Jersey
United States	Teva Investigational Site 14772	Cedarhurst	New York
United States	Teva Investigational Site 14778	Charleston	South Carolina
United States	Teva Investigational Site 14829	Chicago	Illinois
United States	Teva Investigational Site 14763	Cincinnati	Ohio
United States	Teva Investigational Site 14776	Colton	California
United States	Teva Investigational Site 14783	Coral Gables	Florida
United States	Teva Investigational Site 14802	Costa Mesa	California
United States	Teva Investigational Site 14773	Culver City	California
United States	Teva Investigational Site 14782	Dayton	Ohio
United States	Teva Investigational Site 14821	Decatur	Georgia
United States	Teva Investigational Site 14866	Gaithersburg	Maryland
United States	Teva Investigational Site 14859	Garfield Heights	Ohio
United States	Teva Investigational Site 14764	Glen Burnie	Maryland
United States	Teva Investigational Site 14774	Glendale	California
United States	Teva Investigational Site 14787	Hialeah	Florida
United States	Teva Investigational Site 14814	Hialeah	Florida
United States	Teva Investigational Site 14865	Hialeah	Florida
United States	Teva Investigational Site 14867	Hickory	North Carolina
United States	Teva Investigational Site 14805	Hoffman Estates	Illinois
United States	Teva Investigational Site 14861	Homestead	Florida
United States	Teva Investigational Site 14801	Houston	Texas
United States	Teva Investigational Site 14807	Irving	Texas
United States	Teva Investigational Site 14817	La Habra	California
United States	Teva Investigational Site 14862	Lake Charles	Louisiana
United States	Teva Investigational Site 14390	Lake Mary	Florida
United States	Teva Investigational Site 14414	Las Vegas	Nevada
United States	Teva Investigational Site 14809	Las Vegas	Nevada
United States	Teva Investigational Site 14799	Lauderhill	Florida
United States	Teva Investigational Site 14771	Lemon Grove	California
United States	Teva Investigational Site 14871	Lincolnwood	Illinois
United States	Teva Investigational Site 14863	Long Beach	California
United States	Teva Investigational Site 14389	Maitland	Florida
United States	Teva Investigational Site 14770	Marietta	Georgia
United States	Teva Investigational Site 14793	Media	Pennsylvania
United States	Teva Investigational Site 14868	Memphis	Tennessee
United States	Teva Investigational Site 14400	Miami	Florida
United States	Teva Investigational Site 14832	Miami	Florida
United States	Teva Investigational Site 14875	Miami	Florida
United States	Teva Investigational Site 14869	Monroe	Louisiana
United States	Teva Investigational Site 14816	Montclair	California
United States	Teva Investigational Site 14876	New York	New York
United States	Teva Investigational Site 14415	Norcross	Georgia
United States	Teva Investigational Site 14810	North Miami	Florida
United States	Teva Investigational Site 14786	Oakland	California
United States	Teva Investigational Site 14827	Oceanside	California
United States	Teva Investigational Site 14777	Orange	California
United States	Teva Investigational Site 14391	Phoenix	Arizona
United States	Teva Investigational Site 14815	Pico Rivera	California
United States	Teva Investigational Site 14393	Plano	Texas
United States	Teva Investigational Site 14856	Richardson	Texas
United States	Teva Investigational Site 14796	Rogers	Arkansas
United States	Teva Investigational Site 14791	Saint Louis	Missouri
United States	Teva Investigational Site 14813	Saint Louis	Missouri
United States	Teva Investigational Site 14826	Saint Louis	Missouri
United States	Teva Investigational Site 14785	San Bernardino	California
United States	Teva Investigational Site 14818	San Diego	California
United States	Teva Investigational Site 14401	Scottsdale	Arizona
United States	Teva Investigational Site 14780	Staten Island	New York
United States	Teva Investigational Site 14860	Tampa	Florida
United States	Teva Investigational Site 14788	Torrance	California
United States	Teva Investigational Site 14405	Tucson	Arizona
United States	Teva Investigational Site 14396	W. Miami	Florida

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  France,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants Who Were Withdrawn From the Treatment	The number of participants who were withdrawn from the treatment due to any reason has been reported. The safety analysis set included all participants who received at least 1 dose of TV46000 in TV-46000-CNS-30072 study or in TV46000-CNS-30078 study.	Baseline up to Week 64
Primary	Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline up to Week 64
Primary	Number of Participants With SAEs	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. The safety analysis set included all participants who received at least 1 dose of TV46000 in TV-46000-CNS-30072 study or in TV46000-CNS-30078 study.	Baseline up to Week 64