NCT04738123已完成3 期
A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adults With DSM-5 Schizophrenia
Karuna Therapeutics30 个研究点 分布在 2 个国家目标入组 256 人开始时间: 2021年4月6日最近更新:
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
- 256
- 试验地点
- 30
- 主要终点
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5
研究概览
简要总结
This is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicenter inpatient study to examine the efficacy and safety of KarXT in adult subjects who are acutely psychotic with a Diagnostic and Statistical Manual Fifth Edition (DSM-5) diagnosis of schizophrenia. The primary objective of the study is to assess the efficacy of KarXT (a fixed combination of xanomeline 125 mg and trospium chloride 30 mg twice daily [BID]) versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores in adult inpatients with a DSM-5 diagnosis of schizophrenia. The secondary objectives of the study are to evaluate improvement in disease severity and symptoms, safety and tolerability, and pharmacokinetics in adult inpatients with a DSM-5 diagnosis of schizophrenia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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, inclusive, at screening.
- •Subject is capable of providing informed consent.
- •A signed informed consent form must be provided before any study assessments are performed.
- •Subject must be fluent (oral and written) in English or local language to consent
- •Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.
- •Subject is experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 2 months before screening.
- •The subject requires hospitalization for this acute exacerbation or relapse of psychotic symptoms.
- •If already an inpatient at screening, has been hospitalized for less than 2 weeks for the current exacerbation at the time of screening.
- •Positive and Negative Syndrome Scale total score between 80 and 120, inclusive. Score of ≥4 (moderate or greater) for ≥2 of the following Positive Scale (P) items:
- •Item 1 (P1; delusions)
- •Item 2 (P2; conceptual disorganization)
- •Item 3 (P3; hallucinatory behavior)
- •Item 6 (P6; suspiciousness/persecution)
- •Subjects with no change (improvement) in PANSS total score between screening and baseline (Day -1) of more than 20%.
- •Subject has a CGI-S score of ≥4 at screening and baseline (Day -1) visits.
- •Subject will have been off lithium therapy for at least 2 weeks before baseline and free of all oral antipsychotic medications for at least 5 half-lives or 1 week, whichever is longer, before baseline (Day -1).
- •Subjects taking a long-acting injectable antipsychotic could not have received a dose of medication for at least 12 weeks (24 weeks for INVEGA TRINZA) before baseline visit (Day -1).
- •Subject is willing and able to be confined to an inpatient setting for the study duration, follow instructions, and comply with the protocol requirements.
- •BMI must be ≥18 and ≤40 kg/m
- •Subject resides in a stable living situation and is anticipated to return to that same stable living situation after discharge, in the opinion of the investigator.
- •Subject has an identified reliable informant/caregiver.
- •Women of childbearing potential, or men with sexual partners of childbearing potential, must be able and willing to use at least 1 highly effective method of contraception during the study and for 30 days after the last dose of study drug. Sperm donation is not allowed for 30 days after the final dose of study drug.
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). Symptoms of mild mood dysphoria or anxiety are allowed as long as these symptoms are not the primary focus of treatment. A screening subject with mild substance abuse disorder within the 12 months before screening must be discussed and agreed upon with the medical monitor before they can be allowed into the study.
- •Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia.
- •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.
- •Subjects with 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 on the physical examination, medical history, ECG, or clinical laboratory results at screening.
- •Subjects cannot currently (within 5 half-lives or 1 week, whichever is longer, before baseline [Day -1]) be receiving oral antipsychotic medications; monoamine oxidase inhibitors; anticonvulsants (eg, lamotrigine, Depakote); tricyclic antidepressants (eg, imipramine, desipramine); selective serotonin reuptake inhibitors; or any other psychoactive medications except for as needed anxiolytics (eg, lorazepam, chloral hydrate).
- •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.
- •Positive test for coronavirus (COVID-19) within 2 weeks before screening and at screening.
- •Subjects with 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) during the 90 days before screening.
- •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) or required clozapine within the last 12 months.
- •Subjects with prior exposure to KarXT.
- •Subjects who experienced any adverse effects due to xanomeline or trospium.
- •Participation in another clinical study in which the subject received an experimental or investigational drug agent within 3 months before screening.
- •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)
Placebo
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 5
时间窗: From baseline up to Week 5
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of participants with schizophrenia and is widely used in the study of antipsychotic therapy. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility, and the negative symptoms in schizophrenia are the diminution or loss of normal functions. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. The PANSS Total Score is then the sum of the positive, negative, and general psychopathology symptom scores. Baseline is defined as the PANSS score at screening.
次要结局
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Positive Score at Week 5(From baseline up to Week 5)
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Negative Score at Week 5(From baseline up to Week 5)
- Positive and Negative Syndrome Scale (PANSS) Negative Marder Factor Score Change From Baseline at Week 5(From baseline up to Week 5)
- Clinical Global Impression-Severity (CGI-S) Score Change From Baseline at Week 5(From baseline up to Week 5)
- Number of Participants Who Achieve >=30% Reduction in Positive and Negative Symptoms Scale (PANSS) Total Score From Baseline to Week 5(From baseline up to Week 5)
- Number of Participants Experiencing Adverse Events (AEs)(From first dose up to Day 42)
- Number of Participants Experiencing Cholinergic Symptom Adverse Event(From first dose up to Day 42)
- Change From Baseline in Simpson-Angus Scale Total Score (SAS)(From baseline up to week 5)
- Change From Baseline in Barnes Akathisia Rating Scale (BARS) Total Score(From baseline up to week 5)
- Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score(From baseline up to week 5)
- Number of Participants Who Experienced Weight Change(From baseline up to week 5)
- Change From Baseline in Body Mass Index (BMI)(From baseline up to week 5)
- Change From Baseline in Waist Circumference(From baseline up to week 5)
- Change From Baseline in Orthostatic Vital Signs - Blood Pressure(From baseline up to week 5)
- Change From Baseline in Orthostatic Vital Signs - Heart Rate(From baseline up to week 5)
- Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate(From baseline up to Day 35 or early termination)
- Number of Participants Experiencing Clinically Significant Abnormal Physical Examination Results(From baseline up to week 5)
- Number of Participants Experiencing Each Suicidal Ideation Scale Category as Per Columbia Suicide Severity Rating Scale (C-SSRS)(From screening up to Day 42)
- Area Under the Plasma Concentration-Time Curve (AUC)(At days 8 and 28)
- Maximum Concentration (Cmax)(At days 8 and 28)
- Time to Maximum Concentration (Tmax)(At days 8 and 28)
- Mean Observed Hemoglobin Levels(From baseline up to Days 21, 35, or early temination)
- Mean Observed Hematocrit Levels(From baseline up to Days 21, 35, or early temination)
- Mean Observed Erythrocyte Levels(From baseline up to Days 21, 35, or early temination)
- Mean Observed Platelets Levels(From baseline up to Days 21, 35, or early temination)
- Mean Observed Leukocytes Levels(From baseline up to Days 21, 35, or early temination)
- Mean Observed Lymphocytes Levels(From baseline up to Days 21, 35, or early temination)
- Mean Observed Activated Partial Thromboplastin Time(From baseline up to Days 21, 35, or early temination)
- Mean Observed Prothrombin Time(From baseline up to Days 21, 35, or early temination)
- Mean Observed Urinalysis - pH(From baseline up to Days 21, 35, or early temination)
- Mean Observed Urinalysis - Prolactin(From baseline up to Days 21, 35, or early temination)
- The Number of Participants With Positive Drug Screen Results(At screening, at Dat -1, and upon return from departure from study site at any time up to Day 42)
- The Number of Participants With Elevated Liver Function Test Results(From screening up to Day 42)
研究者
研究点 (30)
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