Clinical trial NCT03893825: A Study to Test if TV-46000 is Safe for Maintenance Treatment of Schizophrenia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2019-03-28
Enrollment: 336
Sex: ALL
Minimum age (years): 13
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Week 64
measure: Number of Participants With SAEs
timeFrame: Baseline up to Week 64
Secondary outcomes:
Other outcomes:
measure: Number of Participants Who Were Withdrawn From the Treatment
timeFrame: Baseline up to Week 64
Locations:
city: Phoenix
country: United States
facility: Teva Investigational Site 14391
state: Arizona
city: Scottsdale
country: United States
facility: Teva Investigational Site 14401
state: Arizona
city: Tucson
country: United States
facility: Teva Investigational Site 14405
state: Arizona
city: Rogers
country: United States
facility: Teva Investigational Site 14796
state: Arkansas
city: Anaheim
country: United States
facility: Teva Investigational Site 14811
state: California
city: Bellflower
country: United States
facility: Teva Investigational Site 14794
state: California
city: Colton
country: United States
facility: Teva Investigational Site 14776
state: California
city: Costa Mesa
country: United States
facility: Teva Investigational Site 14802
state: California
city: Culver City
country: United States
facility: Teva Investigational Site 14773
state: California
city: Glendale
country: United States
facility: Teva Investigational Site 14774
state: California
city: La Habra
country: United States
facility: Teva Investigational Site 14817
state: California
city: Lemon Grove
country: United States
facility: Teva Investigational Site 14771
state: California
city: Long Beach
country: United States
facility: Teva Investigational Site 14863
state: California
city: Montclair
country: United States
facility: Teva Investigational Site 14816
state: California
city: Oakland
country: United States
facility: Teva Investigational Site 14786
state: California
city: Oceanside
country: United States
facility: Teva Investigational Site 14827
state: California
city: Orange
country: United States
facility: Teva Investigational Site 14777
state: California
city: Pico Rivera
country: United States
facility: Teva Investigational Site 14815
state: California
city: San Bernardino
country: United States
facility: Teva Investigational Site 14785
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 14818
state: California
city: Torrance
country: United States
facility: Teva Investigational Site 14788
state: California
city: Coral Gables
country: United States
facility: Teva Investigational Site 14783
state: Florida
city: Hialeah
country: United States
facility: Teva Investigational Site 14865
state: Florida
city: Hialeah
country: United States
facility: Teva Investigational Site 14787
state: Florida
city: Hialeah
country: United States
facility: Teva Investigational Site 14814
state: Florida
city: Homestead
country: United States
facility: Teva Investigational Site 14861
state: Florida
city: Lake Mary
country: United States
facility: Teva Investigational Site 14390
state: Florida
city: Lauderhill
country: United States
facility: Teva Investigational Site 14799
state: Florida
city: Maitland
country: United States
facility: Teva Investigational Site 14389
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 14875
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 14400
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 14832
state: Florida
city: North Miami
country: United States
facility: Teva Investigational Site 14810
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 14860
state: Florida
city: W. Miami
country: United States
facility: Teva Investigational Site 14396
state: Florida
city: Decatur
country: United States
facility: Teva Investigational Site 14821
state: Georgia
city: Marietta
country: United States
facility: Teva Investigational Site 14770
state: Georgia
city: Norcross
country: United States
facility: Teva Investigational Site 14415
state: Georgia
city: Chicago
country: United States
facility: Teva Investigational Site 14829
state: Illinois
city: Hoffman Estates
country: United States
facility: Teva Investigational Site 14805
state: Illinois
city: Lincolnwood
country: United States
facility: Teva Investigational Site 14871
state: Illinois
city: Lake Charles
country: United States
facility: Teva Investigational Site 14862
state: Louisiana
city: Monroe
country: United States
facility: Teva Investigational Site 14869
state: Louisiana
city: Gaithersburg
country: United States
facility: Teva Investigational Site 14866
state: Maryland
city: Glen Burnie
country: United States
facility: Teva Investigational Site 14764
state: Maryland
city: Saint Louis
country: United States
facility: Teva Investigational Site 14791
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 14813
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 14826
state: Missouri
city: Las Vegas
country: United States
facility: Teva Investigational Site 14809
state: Nevada
city: Las Vegas
country: United States
facility: Teva Investigational Site 14414
state: Nevada
city: Berlin
country: United States
facility: Teva Investigational Site 14792
state: New Jersey
city: Cedarhurst
country: United States
facility: Teva Investigational Site 14772
state: New York
city: New York
country: United States
facility: Teva Investigational Site 14876
state: New York
city: Staten Island
country: United States
facility: Teva Investigational Site 14780
state: New York
city: Hickory
country: United States
facility: Teva Investigational Site 14867
state: North Carolina
city: Beachwood
country: United States
facility: Teva Investigational Site 14416
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 14763
state: Ohio
city: Dayton
country: United States
facility: Teva Investigational Site 14782
state: Ohio
city: Garfield Heights
country: United States
facility: Teva Investigational Site 14859
state: Ohio
city: Media
country: United States
facility: Teva Investigational Site 14793
state: Pennsylvania
city: Charleston
country: United States
facility: Teva Investigational Site 14778
state: South Carolina
city: Memphis
country: United States
facility: Teva Investigational Site 14868
state: Tennessee
city: Houston
country: United States
facility: Teva Investigational Site 14801
state: Texas
city: Irving
country: United States
facility: Teva Investigational Site 14807
state: Texas
city: Plano
country: United States
facility: Teva Investigational Site 14393
state: Texas
city: Richardson
country: United States
facility: Teva Investigational Site 14856
state: Texas
city: Bellevue
country: United States
facility: Teva Investigational Site 14395
state: Washington
city: Bourgas
country: Bulgaria
facility: Teva Investigational Site 59148
city: Kazanlak
country: Bulgaria
facility: Teva Investigational Site 59152
city: Lovech
country: Bulgaria
facility: Teva Investigational Site 59151
city: Novi Iskar
country: Bulgaria
facility: Teva Investigational Site 59149
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59144
city: Varna
country: Bulgaria
facility: Teva Investigational Site 59154
city: Varna
country: Bulgaria
facility: Teva Investigational Site 59150
city: Vratsa
country: Bulgaria
facility: Teva Investigational Site 59146
city: Edmonton
country: Canada
facility: Teva Investigational Site 11169
state: Alberta
city: Calgary
country: Canada
facility: Teva Investigational Site 11171
state: AL
city: Vancouver
country: Canada
facility: Teva Investigational Site 11173
state: British Columbia
city: Chatham
country: Canada
facility: Teva Investigational Site 11170
state: Ontario
city: Montreal
country: Canada
facility: Teva Investigational Site 11174
state: Quebec
city: Clermont Ferrand Cedex 1
country: France
facility: Teva Investigational Site 35259
city: Douai
country: France
facility: Teva Investigational Site 35257
city: Nice cedex 1
country: France
facility: Teva Investigational Site 35260
city: Toulon
country: France
facility: Teva Investigational Site 35256
city: Afula
country: Israel
facility: Teva Investigational Site 80162
city: Ashkelon
country: Israel
facility: Teva Investigational Site 80161
city: Haifa
country: Israel
facility: Teva Investigational Site 80156
city: Hod Hasharon
country: Israel
facility: Teva Investigational Site 80155
city: Ramat Gan
country: Israel
facility: Teva Investigational Site 80157
city: Tel Aviv
country: Israel
facility: Teva Investigational Site 80160
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: