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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03503318
Other study ID # TV46000-CNS-30072
Secondary ID 2018-001619-65
Status Completed
Phase Phase 3
First received
Last updated
Start date April 27, 2018
Est. completion date December 3, 2020

Study information

Verified date February 2023
Source Teva Branded Pharmaceutical Products R&D, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


Recruitment information / eligibility

Status Completed
Enrollment 544
Est. completion date December 3, 2020
Est. primary completion date September 30, 2020
Accepts healthy volunteers No
Gender All
Age group 13 Years to 65 Years
Eligibility Inclusion Criteria: - 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 Exclusion Criteria: - 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


Related Conditions & MeSH terms


Intervention

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

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
United States Teva Investigational Site 14789 Allentown Pennsylvania
United States Teva Investigational Site 14811 Anaheim California
United States Teva Investigational Site 14824 Atlanta Georgia
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 14765 Chicago Illinois
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 14834 Columbus Georgia
United States Teva Investigational Site 14768 Coral Gables Florida
United States Teva Investigational Site 14783 Coral Gables Florida
United States Teva Investigational Site 14767 Costa Mesa California
United States Teva Investigational Site 14802 Costa Mesa California
United States Teva Investigational Site 14773 Culver City California
United States Teva Investigational Site 14766 Dallas Texas
United States Teva Investigational Site 14781 Dallas Texas
United States Teva Investigational Site 14782 Dayton Ohio
United States Teva Investigational Site 14821 Decatur Georgia
United States Teva Investigational Site 14835 Garden Grove California
United States Teva Investigational Site 14764 Glen Burnie Maryland
United States Teva Investigational Site 14774 Glendale California
United States Teva Investigational Site 14836 Hallandale Beach Florida
United States Teva Investigational Site 14787 Hialeah Florida
United States Teva Investigational Site 14814 Hialeah Florida
United States Teva Investigational Site 14805 Hoffman Estates Illinois
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 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 14769 Little Rock Arkansas
United States Teva Investigational Site 14823 Long Beach California
United States Teva Investigational Site 14770 Marietta Georgia
United States Teva Investigational Site 14832 Miami Florida
United States Teva Investigational Site 14816 Montclair California
United States Teva Investigational Site 14820 New Bedford Massachusetts
United States Teva Investigational Site 14784 New York New York
United States Teva Investigational Site 14800 New York New York
United States Teva Investigational Site 14804 New York New York
United States Teva Investigational Site 14833 Norristown Pennsylvania
United States Teva Investigational Site 14810 North Miami Florida
United States Teva Investigational Site 14803 Norwalk California
United States Teva Investigational Site 14786 Oakland California
United States Teva Investigational Site 14797 Oceanside California
United States Teva Investigational Site 14827 Oceanside California
United States Teva Investigational Site 14822 Oklahoma City Oklahoma
United States Teva Investigational Site 14777 Orange California
United States Teva Investigational Site 14831 Orange City Florida
United States Teva Investigational Site 14806 Orlando Florida
United States Teva Investigational Site 14815 Pico Rivera California
United States Teva Investigational Site 14830 Princeton New Jersey
United States Teva Investigational Site 14812 Riverside California
United States Teva Investigational Site 14796 Rogers Arkansas
United States Teva Investigational Site 14798 Saginaw Michigan
United States Teva Investigational Site 14790 Saint Louis Missouri
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 14828 San Diego California
United States Teva Investigational Site 14819 San Marcos California
United States Teva Investigational Site 14779 Santa Ana California
United States Teva Investigational Site 14775 Scranton Pennsylvania
United States Teva Investigational Site 14825 Shreveport Louisiana
United States Teva Investigational Site 14780 Staten Island New York
United States Teva Investigational Site 14837 Tampa Florida
United States Teva Investigational Site 14793 Thorndale Pennsylvania
United States Teva Investigational Site 14788 Torrance California

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Bulgaria, 

Outcome

Type Measure Description Time frame Safety issue
Primary Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set 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). From randomization up to 108 weeks
Secondary Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set 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). From randomization up to 108 weeks
Secondary Proportion of Participants With Impending Relapse 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. Week 24
Secondary Number of Participants Who Maintain Stability at the Endpoint 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. At the endpoint (up to 108 weeks)
Secondary Number of Participants Achieving Remission at the Endpoint 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. At Endpoint (up to 108 weeks)
Secondary Observed Rate of Impending Relapse (Number of Participants With Impending Relapse) at the Endpoint 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. At the Endpoint (up to 108 weeks)
Secondary Time to Impending Relapse (Number of Participants With Impending Relapse) in the Adolescent Participants 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). From randomization up to 108 weeks
Secondary Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment 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. Baseline, endpoint and end of treatment (up to Week 108)
Secondary Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment 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. Baseline, endpoint and end of treatment (up to Week 108)
Secondary Number of Participants With Treatment-Emergent Adverse Events (TEAEs) 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. From randomization up to 120 days after last dose of study drug (up to Week 125)
Secondary Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment 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. Baseline, end of treatment (up to 108 weeks)
Secondary Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment 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. Baseline, end of treatment (up to 108 weeks)
Secondary Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment 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. Baseline, end of treatment (up to 108 weeks)
Secondary Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline 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. Baseline, post-baseline (up to 108 weeks)
Secondary Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment 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. Baseline, end of treatment (up to 108 weeks)
Secondary Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment 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). Baseline, end of treatment (up to 108 weeks)
Secondary 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)
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