2024-510770-25-00已完成3 期
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Adjunctive KarXT in Subjects with Inadequately Controlled Symptoms of Schizophrenia
适应症
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 19
- 主要终点
- Change from Baseline in PANSS total score at Week 6
研究概览
简要总结
To evaluate the efficacy of adjunctive KarXT compared with placebo in the treatment of subjects with inadequately controlled symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS) Total Score
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Subject is aged 18 to 65 years (inclusive) at the time of randomization (Visit 3)
- •PANSS Marder Positive symptom factor ≥ 4 on 2 (or more) items (PANSS items, delusions, hallucinations, grandiosity, suspiciousness and persecution, stereotyped thinking, somatic concern, unusual thought content or lack of judgment and insight), at Screening (Visit 1) and randomization (Day 1, Visit 3)
- •Subjects with ≤ 20-point decrease in PANSS total score between Visit 1 and Visit 3
- •Subject is willing and able to visit the clinic in an outpatient setting for the study duration, follow instructions, and comply with the protocol requirements
- •BMI must be within 18 to 40 kg/m2 (inclusive of both values)
- •Subject resides in a stable living situation, in the opinion of the Investigator
- •Subject has identified a reliable informant/ caregiver willing and able to assist with study activities as needed throughout the subject's participation in the study. The informant does not have to be someone responsible for the subject’s physical or psychiatric well-being. The informant needs to be physically present at the Baseline visit, but and can complete the remaining study visits assessments via phone (as needed and as per local regulations). In Bulgaria, the informant needs to be physically present at the Baseline visit and should be physically present at all study visits where the Investigator determines that his/her input would be beneficial
- •Women of childbearing potential (WOCBP), or men whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of study drug. Sperm donation is not allowed for 30 days after the final dose of the study drug. A female subject is considered to be a WOCBP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). For the definition and list of highly effective methods of contraception, see APPENDIX
- •Subject is capable of providing signed Informed Consent Form (ICF) before any study assessments will be performed. Subject must be fluent in the language of the ICF to consent.
- •Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the Diagnostic Statistical Manual 5 (DSM-5) criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2
- •Subject is currently being treated with stable dosing of monotherapy risperidone, paliperidone, aripiprazole, or their LAI formulations, ziprasidone, lurasidone, or cariprazine and has been taking this treatment with the same dosing regimen for at least 8 weeks at the time of Day 1 (Visit 3) (supported by documentation)
- •The subject has an inadequate response to above antipsychotics that was dosed appropriately (within the label), as defined per inclusion criteria 8 and 9
- •The subject has not required psychiatric hospitalization, incarceration in prison, acute crisis intervention, or other increase in the level of care due to symptom exacerbation within 8 weeks of Screening and is psychiatrically stable in the opinion of the Investigator
- •To be eligible for randomization, subjects need to have detectable levels of background antipsychotic medication (measured at Visit 1)
- •PANSS total score ≥ 70 at Screening (Visit 1) and randomization (Day 1, Visit 3)
- •CGI-S scale with a score ≥ 4 (moderate) at Screening (Visit 1) and randomization (Day1, Visit 3)
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)
- •History of irritable bowel syndrome (with or without constipation) or any serious constipation requiring treatment within the last 6 months
- •Risk of suicidal behavior during the study as determined by the Investigator's clinical assessment and/ or C-SSRS as confirmed by the following: a. Answers "Yes" on items 4 or 5 (C-SSRS – ideation) with the most recent episode occurring within the 2 months before Screening or, b. Answers "Yes" to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before Screening
- •Clinically significant abnormal finding on the physical examination, medical history, ECG (QTcF of > 450 msec in males and > 470 msec in females), or clinical laboratory results at Screening
- •Urine toxicology screen is positive for phencyclidine, amphetamines, opiates, cocaine, or alcohol (clinically significant alcohol use in the opinion of the Investigator)
- •Subject is currently taking, or plans to take while in the study, any prohibited concomitant medication as outlined in APPENDIX 4
- •Pregnant, lactating, or less than 3 months postpartum
- •If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/ Medical Monitor, 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 SARS-CoV-2 (COVID-19) within 2 weeks before or at Screening
- •Subjects with extreme concerns relating to global pandemics, such as COVID-19 that would obscure ratings or be expected to disrupt adherence to trial procedures
- •Unable to taper and discontinue a concomitant medication that would preclude participation in the double-blind adjunctive treatment (e.g., cannot stop anticholinergic)
- •The subject has a history of moderate to severe substance use disorder (other than nicotine) within the past 12 months a. A Screening subject with mild substance use disorder within the 12 months before Screening must be discussed with the Medical Monitor before being allowed into the study b. Subjects who test positive for cannabis at Screening may be permitted to enroll in consultation with the Medical Monitor if the subject's pattern of use is not indicative of a moderate to severe substance use disorder
- •Subjects with prior exposure to KarXT
- •Subjects who experienced any adverse effects due to xanomeline or trospium
- •Subjects who received investigational product as part of a clinical trial within 3 months of Screening
- •Risk of violent or destructive behavior as per Investigator's judgment that would interfere with subject's participation
- •Current involuntary hospitalization or incarceration or on parole/probation, unless approved by the Medical Monitor
- •For all male subjects only, any one of the following: a. History of bladder stones b. History of recurrent urinary tract infections c. Serum prostate specific antigen >10 ng/mL d. An IPSS of 5 (almost always) on either item 1, 3, 5, or 6 e. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9
- •Subject has a history of treatment-resistant schizophrenia defined as: Failure to minimally respond to 2 adequate courses of APD pharmacotherapy Note: Failure to minimally respond is defined as persistence of at symptoms of moderate severity in 2 or more psychotic symptom domains or persistence of severe symptoms in 1 or more psychotic symptom domains despite adequate dose and duration (6 weeks or longer) of APD treatment
- •History of symptom instability > 3 psychiatric hospitalizations over the last 12 months or 2 over the last 6 months
- •Current APD is other than aripiprazole, risperidone, paliperidone, or their LAI formulations, ziprasidone, lurasidone, or cariprazine
- •Subjects who are diagnosed with schizophreniform disorder or are experiencing their first treated episode of schizophrenia
- •Significant or severe medical conditions including pulmonary, cardiovascular, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject or the validity of the study results. Subjects with any of the following laboratory values at Screening (Visit 1) are excluded: a. eGFR < 60 mL/min b. Alanine transaminase or aspartate transaminase (AST) > 1.5 x upper limit of normal (ULN) c. Total bilirubin > 1.5 x ULN (Subjects with Gilbert’s syndrome can be included as long as direct bilirubin is ≤ 1.5 x ULN)
- •Subjects with human immunodeficiency virus, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history, serologies or LFT results
- •History or high risk of urinary retention, gastric retention, or narrow- angle glaucoma as evaluated by the Investigator
结局指标
主要结局
Change from Baseline in PANSS total score at Week 6
Change from Baseline in PANSS total score at Week 6
次要结局
- Change from Baseline in PSP at Week 6
- Change from Baseline in CGI-S at Week 6
- Change from Baseline in PANSS M-Pos Symptom Factor score at Week 6
- Change from Baseline in PANSS M-Neg symptom factor score at Week 6
- Categorical response defined as the proportion of subjects achieving a ≥ 30% improvement in PANSS total score at Week 6
- POM at Week 6
研究者
GSM-CT
Scientific
Karuna Therapeutics Inc.
研究点 (19)
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