Safety Outcomes with the Long-Acting Subcutaneous Antipsychotic TV-46000 in Schizophrenia: A Post Hoc Analysis of Behavioral, Neuromotor, Endocrine, and Cardiometabolic Outcomes from Two Phase 3 Studies.
Christoph U Correll, Helena Knebel, Eran Harary, Roy Eshet, Orna Tohami, Mark Suett, Nir Sharon, Kelli R Franzenburg, John M Kane
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引用次数: 0
Abstract
Background: TV-46000 is a long-acting subcutaneous injectable formulation of risperidone approved for treatment of schizophrenia in adults. The aim of this post hoc safety analysis of the phase 3 TV-46000 RISE (NCT03503318) and SHINE (NCT03893825) studies was to examine specific adverse events (AEs) of interest related to second-generation antipsychotic use in participants receiving TV-46000.
Methods: In RISE, participants with schizophrenia who underwent stabilization on oral risperidone were randomized to TV-46000 once monthly (q1m; dose range 50-125 mg) or once every 2 months (q2m; 100-250 mg) or placebo. In SHINE, newly recruited participants and those who completed the RISE study without relapse (rollover) received TV-46000 q1m or q2m. AEs, laboratory tests, vital signs, electrocardiogram, physical examination, and safety/tolerability assessments were recorded. This post hoc analysis evaluated specific antipsychotic-related AEs of interest and assessments related to affective, behavioral, neuromotor, endocrine, sexual/reproductive, and cardiometabolic safety and tolerability.
Results: In the two phase 3 studies, a total of 653 participants with schizophrenia were randomized to treatment, with 181 participants randomized to placebo in RISE (55 of whom were subsequently randomized to TV-46000 q1m or q2m in SHINE), 363 participants randomized to TV-46000 q1m or q2m in RISE, and 109 de novo participants randomized to TV-46000 q1m or q2m in SHINE. Among the groups in the RISE and SHINE studies, affective and behavioral AEs that occurred in ≥ 2% of participants were schizophrenia, anxiety, psychotic disorder, and depression; all occurred in ≤ 4% of participants in any group. The most common central nervous system or neuromotor AEs were headache (range, 0-6%), insomnia (< 1-6%), akathisia (< 1-4%), extrapyramidal disorder (0-4%), dizziness (0-4%), and somnolence (< 1-4%). Common metabolic-related AEs were weight increase (1-6%), increased appetite (0-3%), and hyperglycemia (0-4%). No cardiovascular AEs occurred in ≥ 2% of participants in any group. No clinically meaningful trends were observed in the results of safety assessments and AEs associated with second-generation antipsychotic use, with the exception of an increase in prolactin levels.
Conclusions: The safety profile of TV-46000 is favorable and consistent with other currently approved oral and long-acting injectable risperidone formulations.
Registration: ClinicalTrials.gov, NCT03503318, 18 April 2018; and NCT03893825; 27 March 2019.
期刊介绍：
CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes:
- Overviews of contentious or emerging issues.
- Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses.
- Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement.
- Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry.
- Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies.
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