Clinical Trial Results:
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
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Summary
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EudraCT number |
2019-000063-24 |
Trial protocol |
FR BG |
Global end of trial date |
02 Dec 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Jun 2022
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First version publication date |
15 Jun 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TV46000-CNS-30078
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03893825 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Teva Branded Pharmaceutical Products R&D, Inc.
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Sponsor organisation address |
145 Brandywine Parkway, West Chester, United States, 19380
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Public contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products R&D, Inc., MedInfo@tevaeu.com
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Scientific contact |
Director, Clinical Research, Teva Branded Pharmaceutical Products R&D, Inc., MedInfo@tevaeu.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Dec 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Dec 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Dec 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to evaluate the long-term safety and tolerability of TV-46000 administered in adult and adolescent participants with schizophrenia.
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Protection of trial subjects |
This study was conducted in full accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Apr 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 300
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Country: Number of subjects enrolled |
Bulgaria: 36
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Worldwide total number of subjects |
336
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EEA total number of subjects |
36
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
3
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Adults (18-64 years) |
322
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants who did not experience relapse and completed Study TV46000-CNS-30072 (NCT03503318) (roll-over participants) and new participants entered this study. Open-label oral risperidone (at dose of 2 to 5 milligrams [mg]/day, based on clinical judgment) for 12 weeks was given to stabilize new participants to the treatment before randomization. | |||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Participants who were treated with TV-46000 once monthly (q1m) or once every 2 months (q2m) during Study TV46000-CNS-30072, continued their assigned treatment. Participants who were treated with placebo during Study TV46000-CNS-30072 were randomized to receive TV-46000 q1m or q2m SC injections equivalent to oral dose on which they were stabilized. | |||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | |||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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TV-46000 q1m | |||||||||||||||||||||||||||||||||
Arm description |
Participants received a subcutaneous (SC) injection of TV-46000 at baseline and every 4 weeks (q4w) thereafter for up to 56 weeks. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
TV-46000
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Investigational medicinal product code |
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Other name |
Risperidone
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
TV-46000 was administered per dose and schedule specified in the arm description.
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Arm title
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TV-46000 q2m | |||||||||||||||||||||||||||||||||
Arm description |
Participants received 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 for up to 56 weeks. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Placebo matched to TV-46000 was administered per schedule specified in the arm description.
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Investigational medicinal product name |
TV-46000
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Investigational medicinal product code |
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Other name |
Risperidone
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
TV-46000 was administered per dose and schedule specified in the arm description.
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Baseline characteristics reporting groups
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Reporting group title |
TV-46000 q1m
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Reporting group description |
Participants received a subcutaneous (SC) injection of TV-46000 at baseline and every 4 weeks (q4w) thereafter for up to 56 weeks. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TV-46000 q2m
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Reporting group description |
Participants received 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 for up to 56 weeks. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
TV-46000 q1m
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Reporting group description |
Participants received a subcutaneous (SC) injection of TV-46000 at baseline and every 4 weeks (q4w) thereafter for up to 56 weeks. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. | ||
Reporting group title |
TV-46000 q2m
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Reporting group description |
Participants received 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 for up to 56 weeks. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. | ||
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End point title |
Number of Participants With Adverse Events (AEs) [1] | ||||||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 64
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis is descriptive in nature. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants With Serious Adverse Events [2] | |||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 64
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis is descriptive in nature. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants who Were Withdrawn From the Treatment | |||||||||||||||||||||||||||||||||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Baseline to Week 64
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 64
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Adverse event reporting additional description |
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. No study drug was administered during the open-label stabilization period. All treatment-emergent adverse events are presented.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
TV-46000 q1m
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Reporting group description |
Participants received an SC injection of TV-46000 at baseline and q4w thereafter for up to 56 weeks. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TV-46000 q2m
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Reporting group description |
Participants received an SC injection of TV-46000 at baseline and q8w thereafter, and a placebo SC injection 4 weeks after baseline and q8w thereafter for up to 56 weeks. The maximal dose administered to adult participants was comparable to an oral risperidone dose of 5 mg/day, and the maximal dose administered to adolescents was comparable to 4 mg/day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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03 Jun 2020 |
The following major procedural changes (not all-inclusive) were made to the protocol:
- COVID-19 pandemic-related operational updates were added to the study as a new appendix.
- To avoid duplication and reduce participant burden, many of the baseline procedures and assessments outlined in this protocol related to the roll-over participants, were performed in the end of treatment visit of study 30072, and the results were transferred to this study's clinical database.
- The volume of collected blood samples was corrected accordingly.
- The biomarker sample collection became optional.
- Gender was removed as a stratification factor for randomization of new participants and roll-over participants previously assigned to placebo.
- Various clarifications were made, for example, blinding of personnel to the study treatment assignments in studies TV46000-CNS-30072 and TV46000-CNS-30078 (especially with regard to those also involved in the conduct of study TV46000-CNS-30072).
- Since pin-pointing the onset of schizophrenia in adolescents is difficult, the time since the diagnosis of schizophrenia in the inclusion criterion for adolescents (aged 13-17) was reduced to 6 months to better align with the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, and the requirement for relapse in the last 24 months was removed due to the short time since diagnosis. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
