Trial Outcomes & Findings for A Study to Test if TV-46000 is Safe for Maintenance Treatment of Schizophrenia (NCT NCT03893825)

Last Updated: 2022-12-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

336 participants

Primary outcome timeframe

Baseline up to Week 64

Results posted on

2022-12-07

Participant Flow

Participants who did not experience a relapse and completed Study TV46000-CNS-30072 (NCT03503318) (roll-over participants) and new participants entered this study. Open-label oral risperidone (at a dose of 2 to 5 milligrams \[mg\]/day, based on clinical judgment) for 12 weeks was given to stabilize new participants to the treatments before randomization.

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 in 1:1 to receive TV-46000 q1m or q2m subcutaneous (SC) injections at equivalent to oral dose on which they were stabilized.

Participant milestones

Participant milestones
Measure	TV-46000 q1m Participants received an 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.	TV-46000 q2m 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.
Overall Study STARTED	174	162
Overall Study Received at Least 1 Dose of Study Drug	172	162
Overall Study COMPLETED	135	122
Overall Study NOT COMPLETED	39	40

Reasons for withdrawal

Reasons for withdrawal
Measure	TV-46000 q1m Participants received an 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.	TV-46000 q2m 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.
Overall Study Death	2	1
Overall Study Adverse Event	0	2
Overall Study Withdrawal by Subject	19	21
Overall Study Protocol deviation	1	0
Overall Study Lost to Follow-up	10	10
Overall Study Other than specified	7	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TV-46000 q1m n=174 Participants 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.	TV-46000 q2m n=162 Participants 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.	Total n=336 Participants Total of all reporting groups
Age, Continuous	51.3 years STANDARD_DEVIATION 10.28 • n=99 Participants	49.8 years STANDARD_DEVIATION 11.51 • n=107 Participants	50.6 years STANDARD_DEVIATION 10.90 • n=206 Participants
Sex: Female, Male Female	61 Participants n=99 Participants	59 Participants n=107 Participants	120 Participants n=206 Participants
Sex: Female, Male Male	113 Participants n=99 Participants	103 Participants n=107 Participants	216 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	56 Participants n=99 Participants	51 Participants n=107 Participants	107 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	118 Participants n=99 Participants	110 Participants n=107 Participants	228 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Race · White	80 Participants n=99 Participants	67 Participants n=107 Participants	147 Participants n=206 Participants
Race/Ethnicity, Customized Race · Black or African American	91 Participants n=99 Participants	90 Participants n=107 Participants	181 Participants n=206 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Race · Not reported	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 64

Population: 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.

Outcome measures

Outcome measures
Measure	TV-46000 q1m n=172 Participants 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.	TV-46000 q2m n=162 Participants 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.
Number of Participants With Adverse Events (AEs)	64 Participants	74 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 64

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TV-46000 q1m n=172 Participants 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.	TV-46000 q2m n=162 Participants 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.
Number of Participants With SAEs	8 Participants	11 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 64

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TV-46000 q1m n=172 Participants 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.	TV-46000 q2m n=162 Participants 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.
Number of Participants Who Were Withdrawn From the Treatment Death	2 Participants	1 Participants
Number of Participants Who Were Withdrawn From the Treatment Adverse event	2 Participants	5 Participants
Number of Participants Who Were Withdrawn From the Treatment Withdrawal by participant	21 Participants	25 Participants
Number of Participants Who Were Withdrawn From the Treatment Non-compliance with study drug	1 Participants	0 Participants
Number of Participants Who Were Withdrawn From the Treatment Protocol deviation	2 Participants	1 Participants
Number of Participants Who Were Withdrawn From the Treatment Lost-to-follow up	5 Participants	7 Participants
Number of Participants Who Were Withdrawn From the Treatment Lack of efficacy	1 Participants	0 Participants
Number of Participants Who Were Withdrawn From the Treatment Relapse	3 Participants	3 Participants
Number of Participants Who Were Withdrawn From the Treatment Other	11 Participants	11 Participants

Adverse Events

TV-46000 q1m

Serious events: 8 serious events

Other events: 10 other events

Deaths: 2 deaths

TV-46000 q2m

Serious events: 11 serious events

Other events: 12 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	TV-46000 q1m n=172 participants at risk 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.	TV-46000 q2m n=162 participants at risk 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.
General disorders Injection site nodule	1.7% 3/172 • Number of events 6 • Baseline up to Week 64 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.	5.6% 9/162 • Number of events 13 • Baseline up to Week 64 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.
General disorders Injection site pain	5.2% 9/172 • Number of events 24 • Baseline up to Week 64 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.	4.3% 7/162 • Number of events 23 • Baseline up to Week 64 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.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products R&D, Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER

Measure	TV-46000 q1m n=172 participants at risk 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.	TV-46000 q2m n=162 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/172 • Baseline up to Week 64 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.	0.62% 1/162 • Number of events 1 • Baseline up to Week 64 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.
Cardiac disorders Acute myocardial infarction	0.00% 0/172 • Baseline up to Week 64 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.	0.62% 1/162 • Number of events 1 • Baseline up to Week 64 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.
Cardiac disorders Angina pectoris	0.00% 0/172 • Baseline up to Week 64 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.	0.62% 1/162 • Number of events 1 • Baseline up to Week 64 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.
Cardiac disorders Atrial fibrillation	0.58% 1/172 • Number of events 1 • Baseline up to Week 64 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.	0.00% 0/162 • Baseline up to Week 64 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.
Cardiac disorders Myocardial infarction	0.58% 1/172 • Number of events 1 • Baseline up to Week 64 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.	0.00% 0/162 • Baseline up to Week 64 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.
Metabolism and nutrition disorders Hyperglycaemia	0.58% 1/172 • Number of events 1 • Baseline up to Week 64 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.	0.62% 1/162 • Number of events 1 • Baseline up to Week 64 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.
Nervous system disorders Cerebrovascular accident	0.58% 1/172 • Number of events 1 • Baseline up to Week 64 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.	0.00% 0/162 • Baseline up to Week 64 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.
Psychiatric disorders Depression	0.00% 0/172 • Baseline up to Week 64 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.	0.62% 1/162 • Number of events 1 • Baseline up to Week 64 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.
Psychiatric disorders Major depression	0.58% 1/172 • Number of events 1 • Baseline up to Week 64 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.	0.00% 0/162 • Baseline up to Week 64 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.
Psychiatric disorders Panic attack	0.00% 0/172 • Baseline up to Week 64 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.	0.62% 1/162 • Number of events 1 • Baseline up to Week 64 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.
Psychiatric disorders Psychotic disorder	0.00% 0/172 • Baseline up to Week 64 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.	0.62% 1/162 • Number of events 1 • Baseline up to Week 64 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.
Psychiatric disorders Schizophrenia	0.58% 1/172 • Number of events 1 • Baseline up to Week 64 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.	1.2% 2/162 • Number of events 2 • Baseline up to Week 64 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.
Psychiatric disorders Self-injurious ideation	0.00% 0/172 • Baseline up to Week 64 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.	0.62% 1/162 • Number of events 1 • Baseline up to Week 64 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.
Psychiatric disorders Substance-induced psychotic disorder	0.58% 1/172 • Number of events 1 • Baseline up to Week 64 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.	0.00% 0/162 • Baseline up to Week 64 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/172 • Baseline up to Week 64 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.	0.62% 1/162 • Number of events 1 • Baseline up to Week 64 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.
Vascular disorders Deep vein thrombosis	0.58% 1/172 • Number of events 1 • Baseline up to Week 64 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.	0.00% 0/162 • Baseline up to Week 64 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.