A Phase 1b, Multicenter, Randomized, Double-Blind, Dose-Escalation, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, And Early Signs of Efficacy of Orally Administered LTX-001 As Monotherapy in Adult Participants With Acute Exacerbation of Schizophrenia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 25
- 主要终点
- Safety and Tolerability - Adverse Events
研究概览
简要总结
The purpose of this clinical trial is to learn whether the investigational drug LTX-001 is safe and well tolerated in adults with a diagnosis of schizophrenia who are having a recent worsening of their symptoms (an acute exacerbation). Additional questions it aims to answer are:
- how does the amount of the study drug in the body change over time (pharmacokinetics)
- how does the study drug affect the symptoms of schizophrenia
- how do certain markers in the blood change after administration of LTX-001 (pharmacodynamics)
Researchers will compare different dose levels of LTX-001 to an inactive product (placebo) to see what differences there are between the two treatments.
After successfully screening for the study, participants will stay in a research unit for about five weeks and return one week later for a follow-up visit.
详细描述
After providing informed consent, eligible participants will be asked to visit the study site 3 times and stay overnight for 35 nights (up to 49 nights if up to 14 days of antipsychotic washout is applicable). Procedures will include:
- A review of medical history and medications
- Physical exams, including a neurologic (nervous system) assessment
- Electrocardiograms (a measure of the heart's electrical activity)
- Blood and urine collection
- Psychiatric assessments including the Mini International Neuropsychiatric Exam (MINI), the Brief Assessment of Cognition in Schizophrenia (BACS), and the Positive and Negative Syndrome Scale (PANSS)
- Overall assessment of status via the Clinical Global Impression Scale - Severity (CGI-S)
- Assessment of extrapyramidal symptoms (EPS) as assessed by the Modified Simpson-Angus Scale (M-SAS), the Abnormal Involuntary Movement Scale (AIMS) and the Barnes Akathisia Rating scale (BARS)
- Assessment of suicidality risk via the Columbia Suicidality Severity Rating Scale (C-SSRS)
- Quantitative electroencephalography (qEEG) assessments
- Ophthalmologic examinations
- Administration of the study drug (or placebo) by mouth
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI > 17.5 and < 38.0 kg/m2 and a total body weight > 50.0 kg (110 lbs)
- •Primary diagnosis of schizophrenia per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5-TR)
- •Experiencing an acute exacerbation or relapse of symptoms, with onset less than 2 months prior to screening for the study
- •PANSS total score ≥ 80 at the time of screening for the study
- •Not currently on antipsychotic medication, or is willing to discontinue all prohibited psychotropic medications prior to and during the trial period
- •Sexually active adults must be willing to use an acceptable contraceptive method throughout the study
排除标准
- •Evidence of organ dysfunction or any clinically significant abnormal finding at physical examination
- •History of treatment resistance (e.g., failure to respond to ≥ 2 adequate antipsychotic trials) or failure to respond to use of clozapine
- •Current DSM-5-TR diagnosis other than schizophrenia
- •Pregnant or lactating female
- •Substance use disorder within 1 year prior to screening or recreational use of drugs within 3 months prior to screening
- •Moderate to severe alcohol use disorder as per DSM-5-TR within the past year or excessive use of alcohol within 12 months prior to screening
- •Positive testing for human immunodeficiency virus (HIV)-1 and -2 antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody at screening
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Drug)
LTX-001 twice daily
LTX-001
干预措施: LTX-001 twice daily (Drug)
LTX-001 once daily
LTX-001
干预措施: LTX-001 once daily (Drug)
结局指标
主要结局
Safety and Tolerability - Adverse Events
时间窗: Screening through Day 42
Incidence and severity of treatment-emergent adverse events (TEAEs), and treatment-emergent serious adverse events (TESAEs).
Safety and Tolerability - Clinical Laboratory Tests
时间窗: Screening through Day 42
Clinical laboratory tests (including serum chemistry, hematology, urinalysis)
Safety and Tolerability - Electrocardiograms (ECG)
时间窗: Screening through Day 42
ECGs will measure heart rate (HR), QRS complex and QT, QTcF, and PR intervals
Safety and Tolerability - Physical and Neurological Exams
时间窗: Screening through Day 42
Physical and neurological exams will be performed periodically to ensure participant safety.
Safety and Tolerability - Suicidality
时间窗: Screening through Day 42
Suicidality as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Safety and Tolerability - Extrapyramidal Symptoms
时间窗: Screening through Day 42
Extrapyramidal symptoms (EPS) as assessed by the Modified Simpson-Angus Scale (M-SAS), the Abnormal Involuntary Movement Scale (AIMS) and the Barnes Akathisia Rating scale (BARS)
Vital signs - blood pressure
时间窗: Screening through Day 42
Vital signs will be collected, including blood pressure (mm Hg)
Vital Signs - heart rate
时间窗: Screening through Day 42
Vital signs will be collected, including heart rate (beats per minute)
Vital Signs - respiratory rate
时间窗: Screening through Day 42
Vital signs will be collected, including respiratory rate (breaths per minute)
Vital Signs - body temperature
时间窗: Screening through Day 42
Vital signs will be collected, including body temperature (°C or °F)
Vital Signs - total body weight
时间窗: Screening through Day 42
Vital signs will be collected, including total body weight (kilograms)
Vital Signs - height
时间窗: Screening through Day 42
Vital signs will be collected, including height (centimeters)
Vital Signs - Body Mass Index (BMI)
时间窗: Screening through Day 42
Body Mass Index (BMI) will be calculated using the values of total body weight and height, with the formula BMI = weight in kg/(height in cm)\^2.
Ocular evaluation - Best Corrected Visual Acuity (BCVA)
时间窗: Screening through Day 42
Ocular evaluations, including Best Corrected Visual Acuity (BCVA) will be performed
Ocular evaluation - dilated Color Fundus Photography (CFP)
时间窗: Screening through Day 42
Ocular evaluations, including dilated Color Fundus Photography (CFP) will be performed
Ocular evaluation - Fundus Autofluorescence (FAF)
时间窗: Screening through Day 42
Ocular evaluations, including Fundus Autofluorescence (FAF) will be performed
Ocular evaluation - dilated Optical Coherence Tomography (OCT)
时间窗: Screening through Day 42
Ocular evaluations, including dilated Optical Coherence Tomography (OCT) of the macula and optic nerve will be performed
Ocular evaluation - slit lamp examination
时间窗: Screening through Day 42
Ocular evaluations, including slit lamp examination with measurement of intraocular pressure (IOP) will be performed
次要结局
- Pharmacokinetics of LTX-001 - Single Dose(Days 1 and 8)
- Pharmacokinetics of LTX-001 - Multiple Dose(Days 8 and 35)