A Two-Part, Double-Blind, Placebo-Controlled, Phase I Study of the Safety Pharmacokinetics of Single and Multiple Ascending Doses of CT1812 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Incidence and review of Treatment Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
This is a double-blind, placebo controlled, ascending dose, multi-cohort trial. The study will be conducted in two phases: a single ascending dose (SAD) phase "Part A", followed by a multiple ascending dose (MAD) phase "Part B". In Part A, subjects will receive one dose of study drug. In Part B, subjects within a cohort will receive the same dose daily for 14 days. In both parts, sequential cohorts will be exposed to increasing doses of CT1812 in order to identify the maximum tolerated dose (MTD).
详细描述
Part A - Single Ascending Dose in up to 54 Subjects
Screening procedures will occur on Days -21 to -3. Subjects will be admitted to the clinical research unit for up to 5 days. Administration of a single dose of study drug will occur on Day 1. Following completion of all safety assessments and blood draws for PK analyses, subjects will be discharged on Day 3 or Day 4, depending on cohort.
Double-blind dosing will occur in cohorts 1 through 6. In these cohorts, 6 subjects will receive CT1812 and 2 will receive placebo. Doses will be escalated per protocol.
In cohort 1 only, 2 subjects (1 placebo/1 active CT1812) will be dosed 24 hours prior to the remaining subjects in the cohort. The remaining 6 subjects will be dosed if no safety concerns are identified in the first 2 subjects (the last 6 subjects will be admitted to the research unit one day later than the initial 2 subjects). In cohorts 2 through 7, all subjects will be enrolled and dosed together.
Following completion of each cohort, bioanalytical analyses for CT1812 PK will be performed and plasma Cmax concentrations will be reviewed. Enrollment of additional cohorts and dose escalations will not occur until safety assessments and PK analyses have been completed in the prior cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to provide written informed consent prior to initiation of any study-related procedures.
- •Men and women either ≥ 18 and ≤ 55 years of age or ≥ 65 and ≤75 years of age, depending on cohort.
- •In good health as determined by medical history, physical exam, laboratory examinations, ECG, and vital signs.
- •BMI between 19 and 34 kg/m2, inclusive.
- •Weight between 50 and 100 kg, inclusive.
- •ECG without clinically significant pathologic abnormalities and with QTcB <
- •Normotensive as defined by systolic BP ≤ 150 mmHg and diastolic BP ≤ 90 mmHg.
- •Non-smokers.
- •No suicidal ideation, as demonstrated by a score of "0" on the Columbia Suicide Severity Rating Scale (C-SSRS). Part B Only.
- •Women who are neither pregnant (negative pregnancy test) nor nursing, and are either surgically sterile or postmenopausal.
排除标准
- •Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment that might increase the risk to the subject or confound interpretation of safety observations.
- •Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
- •Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
- •History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
- •Seropositive for human immunodeficiency virus (HIV).
- •History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for Hepatitis B surface antigen [HbsAg] or anti-Hepatitis C [HCV] antibody).
- •Clinically significant abnormalities in specified screening laboratory tests
- •All prescription, over-the-counter and herbal medications are prohibited within 10 days prior to study dosing (with exception of calcium/vitamin D supplements, nasal steroids, ocular medications, and paracetamol at the discretion of the Investigator).
- •Use of an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing in this study.
- •Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs.
- •Psychiatric history of current or past psychosis, bi-polar disorder, clinical depression, or anxiety disorder requiring chronic medication within the past 5 years.
- •History of substance abuse.
- •History of substance or drug dependence or positive urine drug screen at screening visit.
- •History of head injury.
- •Chronic kidney disease.
- •Signs of dementia or cognitive impairment in the elder cohorts.
研究组 & 干预措施
CT1812
In cohorts 1-6, 8 subjects will be enrolled. 6 subjects will receive CT1812. Doses will be escalated in the following sequence: 10mg, 30mg, 90mg, 180mg, 360mg, 650mg.
Should an MTD not be identified, additional cohorts at higher doses may be enrolled. The maximum dose administered will not exceed 1350mg.
干预措施: CT1812 (Drug)
Matching Placebo
In cohorts 1-6, 8 subjects will be enrolled. 6 subjects will receive matching placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence and review of Treatment Emergent Adverse Events [Safety and Tolerability]
时间窗: up to 35 days
Treatment Emergent Adverse Events will be assessed by reviewing: * physical examinations, * monitoring vital signs, * monitoring clinical and laboratory assessments, * monitoring ECGs.
次要结局
未报告次要终点