A Randomised, Double Blind, Placebo Controlled, Single Centre, Three-Part Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of ONO-2808 in Healthy Subjects.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Treatment emergent adverse events (TEAEs) by severity.
研究概览
简要总结
This is a first in human study to determine the safety, tolerability and pharmacokinetics of ONO-2808 in healthy adult participants. The study will be conducted in 3 parts: Part A, a single-ascending dose part with an assessment of the potential food effects in non-Japanese adult participants; Part B, a single dose part to assess the effect of age in non-Japanese elderly participants; and Part C, a multiple-ascending dose part with ONO-2808 administered to healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This is a double-blind study. A sentinel dosing approach will be used in the study at each new ascending dose level in Part A, B, and C. To maintain the blinded nature of the study, the sentinel participants will be randomised to drug or placebo in a 1:1 ratio.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Mentally or legally incapacitated or with significant emotional problems at the time of the Screening visit or expected during the conduct of the study.
- •History or presence of clinically significant medical, surgical or psychiatric condition (including history of suicidal behaviour) or objection by General Practitioner (GP) to participant entering trial.
- •Liver chemistry values above the upper limit of normal (ULN) at Screening or admission.
- •Sensitivity to the study drug.
- •Female who is pregnant or lactating or of childbearing potential.
- •History or presence of alcoholism or drug/chemical/substance abuse.
- •Evidence of poor venous access as assessed by PI.
- •Use of any medication which may affect ONO-2808 pharmacokinetics or pharmacodynamics
- •Current smoker or has smoked (including use of tobacco and/or nicotine-containing products) in the previous 3 months
- •Positive urine drugs of abuse, cotinine or alcohol results at Screening or admission.
- •Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- •Supine resting blood pressure less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg (Part A& C) and less than 90/40 mmHg or greater than 160/90 mmHg (Part B).
- •Supine resting pulse rate lower than 40 beats per minute (bpm) or higher than 100 bpm.
- •Clinically significant history or presence of ECG findings at screening.
- •Use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days or five half-lives (whichever is longer) of first dosing and throughout the study.
- •Consumption or intake of compounds, food or fluids that are known to be a substrate, inducer or inhibitor of CYP450 for 28 days prior to the first dosing and throughout the study.
- •Donation of blood or significant blood loss within 56 days prior to the first dosing, or plasma donation within 7 days prior to the first dosing.
- •Participation in another clinical study within the last 3 months (or 5 half-lives of the study drug, whichever is longer) prior to the first dosing.
- •Objection by PI
- •Participants who are not willing to eat a high fat breakfast
- •Exclusion criteria, applicable to all participants undergoing lumbar puncture for CSF collection (Part A & C):
- •History of significant back pain, significant kyphosis and or scoliosis or other spinal column deformities.
- •History or evidence of fundoscopy suggestive of raised intracranial pressure.
- •History or presence of any allergy or contraindication to the local anaesthetic required for participants undergoing lumbar puncture.
研究组 & 干预措施
ONO-2808 Placebo Part C
Multiple ascending doses of ONO-2808 or placebo orally
干预措施: Placebo (Drug)
ONO-2808 Part A - Fasted
Single ascending doses of ONO-2808 or placebo orally under fasted conditions. Additional descriptive information (including which interventions are administered in each arm) to differentiate each arm from other arms in the clinical trial.
干预措施: ONO-2808 (Drug)
ONO-2808 Placebo Part A- Fasted
Single ascending doses of ONO-2808 or placebo orally under fasted conditions
干预措施: Placebo (Drug)
ONO-2808 Part A - Fed
Single ascending doses of ONO-2808 or placebo orally under fed conditions
干预措施: ONO-2808 (Drug)
ONO-2808 Placebo Part A - Fed
Single ascending doses of ONO-2808 or placebo orally under fed conditions
干预措施: Placebo (Drug)
ONO-2808 Part B
Single dose of ONO-2808 or placebo in elderly female or elderly male healthy volunteers .
干预措施: ONO-2808 (Drug)
ONO-2808 Placebo Part B
Single dose of ONO-2808 or placebo in elderly female or elderly male healthy volunteers
干预措施: Placebo (Drug)
ONO-2808 Part C
Multiple ascending doses of ONO-2808 or placebo orally
干预措施: ONO-2808 (Drug)
结局指标
主要结局
Treatment emergent adverse events (TEAEs) by severity.
时间窗: Part A and B: up to day 7; Part C: up to 17 days.
Number of participants with TEAEs. An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possible causal relationship.
ECG parameters
时间窗: Part A and B: up to day 7; Part C: up to 17 days.
Number of participants with ECG abnormalities
Serious adverse events (SAEs)
时间窗: Part A and B: up to day 7; Part C: up to 17 days.
Number of participants with SAEs. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged hospitalization, life-threatening experience or persistent disability.
Vital signs
时间窗: Part A and B: up to day 7; Part C: up to 17 days
Summary statistics of vital signs and number of participants with clinically significant changes in vital signs including pulse/heart rate, respiratory rate, and blood pressure
Physical examination
时间窗: Part A and B: up to day 7; Part C: up to 17 days
Number of participants with physical examination abnormalities
Neurological examination
时间窗: Part A and B: up to day 7; Part C: up to 17 days.
Number of participants with neurological examination abnormalities
Clinical laboratory tests
时间窗: Part A and B: up to day 7; Part C: up to 17 days
Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis)
Number of participants with suicidal behaviour
时间窗: Part C: up to 17 days
Treatment-emergent suicidal ideation and behaviour will be monitored by using the Columbia Suicide Severity Rating Scale (C-SSRS) and reported.
次要结局
- Pharmacokinetics (AUClast)(Part A & B: Day 1 through Day 7)
- Pharmacokinetics (AUCinf)(Part A & B: Day 1 through Day 7)
- Pharmacokinetics (CL/F)(Part A & B: Day 1 through Day 7)
- Pharmacokinetics (T1/2)(Part A & B: Day 1 through Day 7)
- Pharmacokinetics (Cmax)(Part A & B: Day 1 through Day 7, Part C: Day 1 and 14)
- Pharmacokinetics (Tmax)(Part A & B: Day 1 through Day 7, Part C: Day 1 and 14)
- Pharmacokinetics (AUCtau)(Part C: Day 1 and Day 14)
- Pharmacokinetics (Vz/F)(Part A & B: Day 1 through Day 7)
- Pharmacokinetics (Aetz)(Part A & B: Day 1 through Day 5, Part C: Day 1, 8 & 14)
- Pharmacokinetics (CLR)(Part A & B: Day 1 through Day 5, Part C: Day 1, 8 & 14.)
- Pharmacokinetics (Percentage fe)(Part A & B: Day 1 through Day 5, Part C: Day 1, 8 & 14)
- Distribution of ONO-2808 to the brain in Part A(Part A (in selected fasted cohorts): Day 1 and 2, Part C: Day 1 and Day 14)