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临床试验/NCT04820309
NCT04820309已完成3 期

An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in De Novo Subjects With DSM-5 Schizophrenia

Karuna Therapeutics114 个研究点 分布在 1 个国家目标入组 566 人开始时间: 2021年6月2日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
已完成
发起方
入组人数
566
试验地点
114
主要终点
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a Phase 3, multicenter, 56-week, outpatient, open-label (OL) study to evaluate the long-term safety, tolerability, and efficacy of KarXT in de novo subjects with Diagnostic and Statistical Manual-Fifth Edition (DSM-5) schizophrenia. In this OL study, all subjects will receive KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily [BID]) for up to 52 weeks. The primary objective of the study is to assess the long-term safety and tolerability of KarXT in subjects with a DSM-5 diagnosis of schizophrenia. The secondary objective of this study is to assess the long-term efficacy and characterize the pharmacokinetics of xanomeline and trospium after administration of KarXT.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 65 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Subject is aged 18 to 65 years at screening.
  • •Subject is capable of providing informed consent.
  • •A signed informed consent form (ICF) must be provided before any study assessments are performed.
  • •Subject must be fluent in (oral and written) the language of the ICGF to consent.
  • •Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013) criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.
  • •Subject has not required psychiatric hospitalization, acute crisis intervention, or other increase in level of care due to symptom exacerbation within 8 weeks of screening and is psychiatrically stable in the opinion of the investigator.
  • •PANSS total score ≤ 80 at screening and Baseline Visit B (Day 0).
  • •Clinical Global Impression - Severity (CGI-S) score of ≤ 4 at screening and Baseline Visit B (Day 0).
  • •At the time of screening, or at any time within the 30 days prior to screening, the subject must have received an oral antipsychotic medication daily at a dose and frequency consistent with the drug label.
  • •In the opinion of the investigator, it is clinically appropriate for the subject to discontinue current antipsychotic therapy and initiate experimental treatment with KarXT.
  • •Subject is willing and able, in the opinion of the investigator, to discontinue all antipsychotic medications prior to baseline visit.
  • •Subject has an identified reliable informant willing to be able to address some questions related to certain study visits, if needed. An informant may not be necessary if the subject has been the patient of the investigator for ≥1 year.
  • •At Day 0, subject will have been off lithium therapy for at least 2 weeks and must have discontinued all oral antipsychotic medications.
  • •Subjects taking a long-acting injectable antipsychotic could not have received a dose of medication for at least 12 weeks (24 weeks for paliperidone palmitate) before Day
  • •Body mass index must be ≥ 18 and ≤ 40 kg/m
  • •Subject resides in a stable living situation and is anticipated to remain in a stable living situation for the duration of study enrollment, in the opinion of the investigator.
  • •Women of childbearing potential or men with sexual partners of childbearing potential must be willing and able to use at least 1 highly effective method of contraception during the study and for at least 30 days after the last dose of KarXT. Sperm donation is not allowed for 30 days after the final dose of KarXT.

排除标准

  • •Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening).
  • •Subject has a history of moderate to severe alcohol use disorder or a substance (other than nicotine or caffeine) use disorder within the past 12 months or a positive urine drug screen (UDS) for a substance other than cannabis at screening or baseline.
  • •History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results
  • •Subject has human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or liver function test results.
  • •History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma
  • •History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
  • •Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).
  • •Clinically significant abnormal finding from the physical examination, medical history, ECG, or clinical laboratory results at screening.
  • •Subjects cannot currently (within 5 half-lives before Day 0) be receiving monoamine oxidase inhibitors, anticonvulsants, tricyclic antidepressants, centrally active anticholinergics, or any other psychoactive medications other than daily antipsychotic maintenance therapy. As-needed anxiolytics and/or sleep aids are permitted. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors taken at stable dose may be permitted.
  • •Subject has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) within the past 12 months or having received clozapine within the past 3 years
  • •Pregnant, lactating, or less than 3 months postpartum.
  • •If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the investigator (and/or Sponsor), may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements.
  • •Subjects has tested positive for coronavirus disease 2019 (COVID-19) within 2 weeks of screening.
  • •Subject has extreme concerns relating to global pandemics, such as COVID-19, that preclude study participation.
  • •Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) within the 6 months before screening.
  • •Subject has prior exposure to KarXT.
  • •Risk of violent or destructive behavior.
  • •Current involuntary hospitalization or incarceration.

研究组 & 干预措施

KarXT

Experimental

干预措施: Xanomeline and Trospium Chloride Capsules (Drug)

结局指标

主要结局

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

时间窗: From time of consent to end of study (approximately 400 days)

TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

次要结局

  • Number of Participants With Serious Treatment Emergent Adverse Events (STEAEs)(From time of consent to end of study (approximately 400 days))
  • Number of Participants With TEAE Leading to Study Drug Discontinuation(From time of consent to end of study (approximately 400 days))
  • Change From Baseline in PANSS Total Score at Week 52(At baseline and week 52)
  • Change From Baseline in PANSS Positive Score at Week 52(At baseline and week 52)
  • Change From Baseline in PANSS Negative Score at Week 52(At baseline and week 52)
  • Change From Baseline in PANSS Marder Factor Negative Score at Week 52(At baseline and week 52)
  • Change From Baseline in Clinical Global Impressions-severity (CGI-S) Score Week 52(At baseline and week 52)
  • Percentage of Participants With a ≥30% Reduction in PANSS Total Score at Week 52(At baseline and week 52)
  • Number of Participants With Adverse Events of Special Interest (AESI)(From time of consent to end of study (approximately 400 days))
  • Number of Participants With Anticholinergic and Procholinergic Symptoms(From time of consent to end of study (approximately 400 days))
  • Change From Baseline in Simpson-Angus Rating Scale (SAS)(From time of consent to end of study (approximately 400 days))
  • Change From Baseline in Barnes Akathisia Rating Scale (BARS)(From time of consent to end of study (approximately 400 days))
  • Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS)(From time of consent to end of study (approximately 400 days))
  • Change From Baseline in Body Mass Index (BMI)(From time of consent to end of study (approximately 400 days))
  • Change From Baseline in Waist Circumference(From time of consent to end of study (approximately 400 days))
  • Change From Baseline in Blood Pressure Values(From time of consent to end of study (approximately 400 days))
  • Change From Baseline in Heart Rate(From time of consent to end of study (approximately 400 days))
  • Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments(From time of consent to end of study (approximately 400 days))
  • Number of Participants With Clinically Significant Changes in 12 Lead Electrocardiogram(From time of consent to end of study (approximately 400 days))
  • Number of Participants With Clinically Significant Changes in Physical Examination(From time of consent to end of study (approximately 400 days))
  • Number of Participants With Suicidal Ideation Based on the Columbia Suicide Severity Rating Scale (C-SSRS)(From time of consent to end of study (approximately 400 days))

研究者

发起方
Karuna Therapeutics
申办方类型
Industry
责任方
Sponsor

研究点 (114)

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