Study to Evaluate TV-46000 as Maintenance Treatment in Adult and Adolescent Participants With Schizophrenia
- Registration Number
- NCT03503318
- Lead Sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Brief Summary
The purpose of the study is to evaluate the efficacy, safety, and tolerability of different dose regimens of TV-46000 administered subcutaneously (SC) as compared to placebo during maintenance treatment in adult and adolescent participants with schizophrenia. The study will include male and female participants, 13 to 65 years of age, who have a confirmed diagnosis of schizophrenia, are clinically stable, and are eligible for risperidone treatment
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 544
-
The participant has a diagnosis of schizophrenia for >1 year and has had ≥1 episode of relapse in the last 24 months.
-
The participant has been responsive to an antipsychotic treatment (other than clozapine) in the past year based on discussions with family members or healthcare professionals.
-
The participant has 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 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 drugs 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, or 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
- Additional criteria apply, please contact the investigator for more information
-
The participant has a current clinically significant Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, or amnestic or other cognitive disorders, or borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
-
The participant is currently on clozapine or 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 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 has previously participated in a Teva-sponsored clinical study with TV-46000.
-
The participant is a pregnant or lactating female.
-
The participant has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
-
The participant has used an investigational drug within 3 months prior to screening or has participated in a non-drug clinical trial within 30 days prior to screening.
- Additional criteria apply, please contact the investigator for more information
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants will receive an SC injection of placebo matching to TV-46000 at baseline and every 4 weeks (q4w) thereafter. Participants will continue treatment until they experience a relapse event; meet 1 or more of the study discontinuation or withdrawal criteria; or remain relapse-free during the double-blind phase until the study is terminated. TV-46000 q2m Placebo Participants will receive an SC injection of TV-46000 at baseline and every 8 weeks (q8w) thereafter, and a placebo SC injection 4 weeks after baseline and q8w thereafter. The maximal dose for adult participants is comparable to an oral risperidone dose of 5 mg/day, and the maximal dose for adolescents is comparable to 4 mg/day. Participants will continue treatment until they experience a relapse event; meet 1 or more of the study discontinuation or withdrawal criteria; or remain relapse-free during the double-blind phase until the study is terminated. TV-46000 q1m TV-46000 Participants will receive an SC injection of TV-46000 at baseline and q4w thereafter. The maximal dose for adult participants is comparable to an oral risperidone dose of 5 milligrams (mg)/day, and the maximal dose for adolescents is comparable to 4 mg/day. Participants will continue treatment until they experience a relapse event; meet 1 or more of the study discontinuation or withdrawal criteria; or remain relapse-free during the double-blind phase until the study is terminated. TV-46000 q2m TV-46000 Participants will receive an SC injection of TV-46000 at baseline and every 8 weeks (q8w) thereafter, and a placebo SC injection 4 weeks after baseline and q8w thereafter. The maximal dose for adult participants is comparable to an oral risperidone dose of 5 mg/day, and the maximal dose for adolescents is comparable to 4 mg/day. Participants will continue treatment until they experience a relapse event; meet 1 or more of the study discontinuation or withdrawal criteria; or remain relapse-free during the double-blind phase until the study is terminated.
- Primary Outcome Measures
Name Time Method Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set From randomization up to 108 weeks Relapse was defined as 1 or more of the following items: • Clinical Global Impression-Improvement (CGI-I) of ≥5, and - an increase of any of the 4 Positive and Negative Syndrome Scale (PANSS) items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • Clinical Global Impression-Severity of Suicidality (CGI-SS) of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (number of participants with impending relapse).
- Secondary Outcome Measures
Name Time Method Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment Baseline, end of treatment (up to 108 weeks) The CGI-SS scale provides an overall clinician-rated assessment of the risk of suicidality. The CGI-SS consists of a 5-point scale in Part 1 (the most severe level of suicidality experience) ranging from 1 (not at all suicidal) to 5 (attempted suicide) and a 7-point scale in Part 2 (change in participant suicidality) ranging from 1 (very much improved) to 7 (very much worse).
Proportion of Participants With Impending Relapse Week 24 Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Impending relapse rate at Week 24 was estimated using the Kaplan-Meier product estimate.
Number of Participants Who Maintain Stability at the Endpoint At the endpoint (up to 108 weeks) Stability is defined as meeting all of the following criteria for at least 4 consecutive weeks: outpatient status; PANSS total score ≤80; minimal presence of specific psychotic symptoms on the PANSS, as measured by a score of ≤4 on each of the following items: conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content; Clinical Global Impression of Severity (CGI-S) score ≤4 (moderately ill); and CGI-SS score ≤2 (mildly suicidal) on Part 1 and ≤5 (minimally worsened) on Part 2. The last valid participant assessment was used as the endpoint.
Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set From randomization up to 108 weeks Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (adults and adolescents) (number of participants with impending relapse).
Number of Participants Achieving Remission at the Endpoint At Endpoint (up to 108 weeks) The remission was achieved for participants who did not relapse during the study and for over a period of at least 6 months preceding the endpoint, maintained scores of = 3 on each of the 8 specific PANSS items: P1 (delusions), G9 (unusual thought content), P3 (hallucinatory behavior), P2 (conceptual disorganization), G5 (mannerisms/posturing), N1 (blunted affect), N4 (social withdrawal), and N6 (lack of spontaneity). The last valid participant assessment was used as the endpoint.
Observed Rate of Impending Relapse (Number of Participants With Impending Relapse) at the Endpoint At the Endpoint (up to 108 weeks) Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Observed rate of impending relapse was calculated as the number of participants who relapsed by endpoint divided by the number of participants in each treatment group, using the last valid participant assessment as the endpoint.
Time to Impending Relapse (Number of Participants With Impending Relapse) in the Adolescent Participants From randomization up to 108 weeks Relapse was defined as 1 or more of the following items: • CGI-I of ≥5, and - an increase of any of the 4 PANSS items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (adolescents) (number of participants with impending relapse).
Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment Baseline, endpoint and end of treatment (up to Week 108) The DAI-10 is a 10-item questionnaire to assess 1) subjective experience of drug and 2) attitudes and beliefs toward neuroleptics which may influence compliance in schizophrenia participants. The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a participant who was fully adherent to the prescribed medication answered as "True" and 4 items (2, 5, 6, and 8) that a participant who was fully adherent to the prescribed medication answered as "False." A correct answer was scored +1 and an incorrect answer was scored -1. The total score was the sum of pluses and minuses, which ranged from -10 to 10 in increments of 2. A positive total score indicated a positive subjective response (compliant) and a negative total score indicated a negative subjective response (non-compliance). Higher scores denoted better compliance. The last valid participant assessment was used as the endpoint.
Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment Baseline, endpoint and end of treatment (up to Week 108) The SQLS comprises 33 items categorized in 2 domains: psychosocial feelings (20 items) and cognition and vitality (13 items). The items were scored on a 5-point scale (1 - never, 2 - rarely, 3 - sometimes, 4 - often, 5 - always). Individual domain and total scores were standardized by scoring algorithm to a 0 (best health status) to 100 (worst health status) scale, with higher scores indicating comparatively lower quality of life. The last valid participant assessment was used as the endpoint.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) From randomization up to 120 days after last dose of study drug (up to Week 125) An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs 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.
Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment Baseline, end of treatment (up to 108 weeks) The AIMS is a 14-item scale that includes assessments of orofacial movements, extremity and truncal dyskinesia, examiner's judgment of global severity, subjective measures of awareness of movements and distress, and a yes/no assessment of problems concerning teeth and/or dentures. Total AIMS score is a sum of item 1 through 7. Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 0 (no dyskinesia) to 4 (severe dyskinesia) scale. Total AIMS score for Items 1-7 ranged from 0 to 28; with higher scores indicating greater severity of the condition.
Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment Baseline, end of treatment (up to 108 weeks) The SAS is a 10-item instrument for the assessment of neuroleptic-induced parkinsonism. The items on the scale include measurements of hypokinesia, rigidity, glabellar reflex, tremor, and salivation. Each item was rated on a 5-point scale (0 \[None/Normal\] to 4 \[Extreme/Severe\]). The mean score was calculated by adding the individual item scores and dividing by 10. The total mean score ranged from 0-4, with a higher score indicating greater severity of symptoms.
Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment Baseline, end of treatment (up to 108 weeks) The BARS is an instrument that assesses the severity of drug-induced akathisia. The BARS includes 3 items for rating objective restless movements, subjective restlessness, and any subjective distress associated with akathisia that were scored on a 4-point scale of 0 (normal/no distress) to 3 (constant restlessness/severe distress). Total score was the sum of scores of each item and ranged from 0-9, with higher scores indicating greater severity of akathisia.
Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline Baseline, post-baseline (up to 108 weeks) The C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.
Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment Baseline, end of treatment (up to 108 weeks) The CDSS is specifically designed to assess the level of depression separate from the positive, negative, and EPS in schizophrenia. This clinician-administered instrument consists of 9 items, each rated on a 4-point scale from 0 (absent) to 3 (severe) that were added together to form the total CDSS depression score of the participant. The total score ranged from 0-27, with higher scores indicating greater severity of the condition.
Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone) 1 hour prior to dosing at Baseline (Day 1) and at the end of treatment visit (up to 108 weeks)
Trial Locations
- Locations (81)
Teva Investigational Site 14770
🇺🇸Marietta, Georgia, United States
Teva Investigational Site 14824
🇺🇸Atlanta, Georgia, United States
Teva Investigational Site 14779
🇺🇸Santa Ana, California, United States
Teva Investigational Site 14792
🇺🇸Berlin, New Jersey, United States
Teva Investigational Site 14830
🇺🇸Princeton, New Jersey, United States
Teva Investigational Site 14789
🇺🇸Allentown, Pennsylvania, United States
Teva Investigational Site 14781
🇺🇸Dallas, Texas, United States
Teva Investigational Site 14811
🇺🇸Anaheim, California, United States
Teva Investigational Site 14797
🇺🇸Oceanside, California, United States
Teva Investigational Site 14790
🇺🇸Saint Louis, Missouri, United States
Teva Investigational Site 14784
🇺🇸New York, New York, United States
Teva Investigational Site 59151
🇧🇬Lovech, Bulgaria
Teva Investigational Site 59149
🇧🇬Novi Iskar, Bulgaria
Teva Investigational Site 14817
🇺🇸La Habra, California, United States
Teva Investigational Site 14780
🇺🇸Staten Island, New York, United States
Teva Investigational Site 14807
🇺🇸Irving, Texas, United States
Teva Investigational Site 14772
🇺🇸Cedarhurst, New York, United States
Teva Investigational Site 14793
🇺🇸Thorndale, Pennsylvania, United States
Teva Investigational Site 14833
🇺🇸Norristown, Pennsylvania, United States
Teva Investigational Site 59148
🇧🇬Bourgas, Bulgaria
Teva Investigational Site 14774
🇺🇸Glendale, California, United States
Teva Investigational Site 14800
🇺🇸New York, New York, United States
Teva Investigational Site 59146
🇧🇬Vratsa, Bulgaria
Teva Investigational Site 14782
🇺🇸Dayton, Ohio, United States
Teva Investigational Site 14775
🇺🇸Scranton, Pennsylvania, United States
Teva Investigational Site 14804
🇺🇸New York, New York, United States
Teva Investigational Site 14766
🇺🇸Dallas, Texas, United States
Teva Investigational Site 59152
🇧🇬Kazanlak, Bulgaria
Teva Investigational Site 14818
🇺🇸San Diego, California, United States
Teva Investigational Site 14828
🇺🇸San Diego, California, United States
Teva Investigational Site 14809
🇺🇸Las Vegas, Nevada, United States
Teva Investigational Site 14763
🇺🇸Cincinnati, Ohio, United States
Teva Investigational Site 14801
🇺🇸Houston, Texas, United States
Teva Investigational Site 59150
🇧🇬Varna, Bulgaria
Teva Investigational Site 59154
🇧🇬Varna, Bulgaria
Teva Investigational Site 59144
🇧🇬Sofia, Bulgaria
Teva Investigational Site 14822
🇺🇸Oklahoma City, Oklahoma, United States
Teva Investigational Site 14769
🇺🇸Little Rock, Arkansas, United States
Teva Investigational Site 14796
🇺🇸Rogers, Arkansas, United States
Teva Investigational Site 14794
🇺🇸Bellflower, California, United States
Teva Investigational Site 14802
🇺🇸Costa Mesa, California, United States
Teva Investigational Site 14776
🇺🇸Colton, California, United States
Teva Investigational Site 14835
🇺🇸Garden Grove, California, United States
Teva Investigational Site 14773
🇺🇸Culver City, California, United States
Teva Investigational Site 14803
🇺🇸Norwalk, California, United States
Teva Investigational Site 14771
🇺🇸Lemon Grove, California, United States
Teva Investigational Site 14786
🇺🇸Oakland, California, United States
Teva Investigational Site 14823
🇺🇸Long Beach, California, United States
Teva Investigational Site 14816
🇺🇸Montclair, California, United States
Teva Investigational Site 14827
🇺🇸Oceanside, California, United States
Teva Investigational Site 14815
🇺🇸Pico Rivera, California, United States
Teva Investigational Site 14777
🇺🇸Orange, California, United States
Teva Investigational Site 14785
🇺🇸San Bernardino, California, United States
Teva Investigational Site 14812
🇺🇸Riverside, California, United States
Teva Investigational Site 14819
🇺🇸San Marcos, California, United States
Teva Investigational Site 14788
🇺🇸Torrance, California, United States
Teva Investigational Site 14814
🇺🇸Hialeah, Florida, United States
Teva Investigational Site 14783
🇺🇸Coral Gables, Florida, United States
Teva Investigational Site 14787
🇺🇸Hialeah, Florida, United States
Teva Investigational Site 14832
🇺🇸Miami, Florida, United States
Teva Investigational Site 14836
🇺🇸Hallandale Beach, Florida, United States
Teva Investigational Site 14768
🇺🇸Coral Gables, Florida, United States
Teva Investigational Site 14799
🇺🇸Lauderhill, Florida, United States
Teva Investigational Site 14810
🇺🇸North Miami, Florida, United States
Teva Investigational Site 14831
🇺🇸Orange City, Florida, United States
Teva Investigational Site 14834
🇺🇸Columbus, Georgia, United States
Teva Investigational Site 14805
🇺🇸Hoffman Estates, Illinois, United States
Teva Investigational Site 14821
🇺🇸Decatur, Georgia, United States
Teva Investigational Site 14765
🇺🇸Chicago, Illinois, United States
Teva Investigational Site 14820
🇺🇸New Bedford, Massachusetts, United States
Teva Investigational Site 14764
🇺🇸Glen Burnie, Maryland, United States
Teva Investigational Site 14829
🇺🇸Chicago, Illinois, United States
Teva Investigational Site 14825
🇺🇸Shreveport, Louisiana, 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 14767
🇺🇸Costa Mesa, California, United States
Teva Investigational Site 14798
🇺🇸Saginaw, Michigan, United States
Teva Investigational Site 14806
🇺🇸Orlando, Florida, United States
Teva Investigational Site 14837
🇺🇸Tampa, Florida, United States
Teva Investigational Site 14778
🇺🇸Charleston, South Carolina, United States