A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of Single and Multiple Doses of Orally Administered RDN-929 in Healthy Adult and Elderly Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Number of subjects with adverse events
研究概览
简要总结
A three (3) part study to evaluate the safety, tolerability and PK of RDN-929
详细描述
Part 1 (Randomized, Double Blind):
Up to 6 single ascending doses of RDN-929 are planned to be tested in 6 cohorts of 8 healthy males (Cohort 1:1 to 1:6). Within each cohort subjects will be randomly assigned to receive either a single dose of RDN-929 (6 subjects) or matched placebo (2 subjects).
Part 2 (Open):
Part 2 will consist of 2 crossover treatment periods in one cohort of 12 healthy elderly subjects (at least 3 of each gender), aged 55-80 years. The treatments will be separated by a washout period of at least 7 days. The dose selected for this part of the study will be based on the results of Part 1.
In Period 1, subjects will be randomized to receive a single dose of RDN-929 in either fasted or fed status. In Period 2, subjects will receive a single dose of RDN-929 under the alternate status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy as determined by the Investigator, based on a medical evaluation including medical history physical examination, neurological examination, laboratory tests and cardiac monitoring
- •Men, age 18-54 years inclusive at Screening (Part 1) or men and postmenopausal or surgically sterile women age 55-80
排除标准
- •Any history of major psychiatric disorders, including substance use disorders, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria.
- •Acute suicidality or history of suicidal behavior.
- •Alanine aminotransferase or aspartate aminotransferase levels greater than 1.5 times the upper limit of normal (ULN) at Screening. One retest is allowed.
- •A corrected QT interval measurement corrected according to the Fridericia rule (QTcF) > 450 msec during controlled rest at screening or between screening and first dose administration, or family history of long QT syndrome.
- •Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, in the judgement of the Investigator or Medical Monitor, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy.
- •A clinically significant vital signs abnormality at screening or between screening and first dose administration. This includes, but is not limited to, the following, in the supine position: (a) systolic blood pressure < 90 or >150 mmHg, (b) diastolic blood pressure <50 or > 95 mmHg, or (c) heart rate < 45 or >100 beats per minute.
研究组 & 干预措施
Cohort 1:1 - 1:6 placebo
Placebo single dose capsule
干预措施: Placebo oral capsule (Drug)
Cohort 2:1
Fed/Fast RDN-929
干预措施: RDN-929 TBD dose (Drug)
Cohort 1:1 - 1:6 RDN-929
RDN-929 single dose capsule
干预措施: RDN-929 (Drug)
Cohort 3:1- 3:4 RDN-929
RDN-929 multiple dose capsules once daily for 12 days
干预措施: RDN-929 (Drug)
Cohort 3:1- 3:4 placebo
placebo multiple dose capsules once daily for 10 days
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Number of subjects with adverse events
时间窗: Screening to end of study, up to 7 weeks
Listing and summary of AE incidence
Number of subjects with Physical exam findings
时间窗: Screening to end of study, up to 7 weeks
Listing of clinically significant changes in PE findings
Number of subjects with Clinical safety lab changes
时间窗: Screening to end of study, up to 7 weeks
Listing and change from baseline to end of study
Number of subjects with Systolic blood pressure changes
时间窗: Screening to end of study, up to 7 weeks
Listing and change from baseline to end of study
Number of subjects with Heart rate changes
时间窗: Screening to end of study, up to 7 weeks
Listing and change from baseline to end of study
Number of subjects with 12 Lead ECG changes
时间窗: Screening to end of study, up to 7 weeks
Change in 12-lead ECG parameters from baseline to end of study
Number of subjects with 3 Lead ECG findings
时间窗: Predose to 8 hours post dose on Day 1 (Parts 1 and 2) and Days 1 and 12 (Part 3)
Listing of findings
Number of subjects with C-SSRS changes
时间窗: Baseline to end of study (Part 3 only), up to 7 weeks
Listing of results
Number of subjects with Visual analogue scale changes
时间窗: Baseline to end of study for Part 1 and 3, up to 7 weeks
VAS for headache and nausea
次要结局
- Maximum observed plasma concentration, Cmax(Predose to 48 hours post first and last dose, up to 2 days (Parts 1 and 2) and 2 weeks (Part 3))
- Time to reach maximum observed plasma concentration, Tmax(Predose to 48 hours post first and last dose, up to 2 days (Parts 1 and 2) and 2 weeks (Part 3))
- Area Under the plasma concentration time curve, AUC(Predose to 48 hours post last dose, up to 2 days (Parts 1 and 2) and 2 weeks (Part 3))