A Phase I, Randomized Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study to Determine the Safety, Tolerability and Pharmacokinetics (PK) of IkT-148009 in Older Adult and Elderly Healthy Volunteers With Extension Into Parkinson's Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 4
- 主要终点
- Pharmacokinetic AUC of IkT-148009
研究概览
简要总结
This study investigates the safety and tolerability of drug IkT-148009 in healthy elderly volunteers (55 to 70 years old). This first-in-human study is designed in 3 parts. In Part A, healthy participants will take a single, oral dose of IkT-148009 or placebo. Part A participants will be at the study site for approximately 4 days. In Part B, healthy participants will take an oral dose of IkT-148009 once a day for 7 days. Part B participants will be at the study site for approximately 12 days. In Part C, Parkinson's patients will take an oral dose of IkT-148009 once a day for 7 days. Part C participants will be at the study site for approximately 12 days.
详细描述
This is a randomized, Phase 1 study in older adult or elderly healthy volunteer subjects with subsequent extension into Parkinson patients to identify the safety, tolerability, maximum tolerated dose (MTD) and the pharmacokinetic (PK) profile of IkT-148009 capsules given as single or multiple doses.
In Part A (SAD) cohorts will consist of eight (8) subjects, six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo. Sentinel dosing will be employed on the first day of each cohort, with one subject randomized to receive IkT-148009 and the other placebo. These two subjects in each cohort will be monitored for 48 hours after dosing before deciding to dose the remainder of the cohort. The other six subjects in the first cohort will be dosed approximately 48 hours later. Each cohort will be monitored for at least 48 hours before deciding whether to administer drug to the sentinel pair for the next cohort. Each cohort will be dosed at approximately weekly intervals to allow adequate time for collection and review of safety and PK data.
A Safety Review Committee (SRC) will evaluate all available safety, tolerability, and PK data for each cohort. Escalation to a next dose will be undertaken only after these data have been reviewed by the SRC and agreement reached that it is safe to increase the dose. The SRC will not receive any unblinded PK data unless they agree to unblind a subject and/or cohort based on the completed safety review.
In Part B (MAD) cohorts will consist of eight (8) subjects, six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo daily for up to seven consecutive days. Subjects in each cohort will be observed for 48 hours after their last dose before deciding to initiate the next (higher dose) cohort. Each cohort will be dosed at approximately weekly intervals in order to allow adequate time for collection and review of safety and PK data. At the discretion of the SRC, MAD cohorts may be added consisting of eligible participants with Parkinson's Disease (Part C).
In Part C (MAD with Parkinson's Disease) eligible PD participants will arrive the evening before initiation of study drug dosing. No Parkinsonism medications will be given after midnight, the following morning potential participants will be clinically assessed in the practically-defined OFF state using MDS-UPDRS Part III. Cohorts will consist of eight (8) subjects, six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo daily for up to seven consecutive days. Subjects in each cohort will be observed for 48 hours after their last dose before deciding to initiate the next (higher dose) cohort. Each cohort will be dosed at approximately weekly intervals in order to allow adequate time for collection and review of safety and PK data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 70 Years（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
- 未提供
研究组 & 干预措施
Single Ascending Dose (SAD)
In Part A, cohorts will consist of eight (8) subjects; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
干预措施: IkT-148009 (Drug)
Single Ascending Dose (SAD)
In Part A, cohorts will consist of eight (8) subjects; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
干预措施: Placebo (Drug)
Multiple Ascending Dose (MAD)
In Part B, cohorts will consist of eight (8) subjects; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
干预措施: IkT-148009 (Drug)
Multiple Ascending Dose (MAD)
In Part B, cohorts will consist of eight (8) subjects; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
干预措施: Placebo (Drug)
Multiple Ascending Dose (MAD) Parkinson's patients
In Part C, cohorts will consist of eight (8) patients; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
干预措施: IkT-148009 (Drug)
Multiple Ascending Dose (MAD) Parkinson's patients
In Part C, cohorts will consist of eight (8) patients; six (6) of whom will receive treatment with IkT-148009 and two (2) with matching placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Pharmacokinetic AUC of IkT-148009
时间窗: Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.
Area under the concentration-time curve (AUC0-∞)
Pharmacokinetic Cmax of IkT-148009
时间窗: Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.
Maximum plasma concentration (Cmax)
Safety: incidence of abnormal vital sign measurements
时间窗: Safety assessments performed from Day 1 through Day 14
body temperature by mouth, blood pressure, pulse rate, pulse oximetry, respiration rate
Safety: incidence of abnormal electrocardiogram [ECG]
时间窗: Safety assessments performed from Day 1 through Day 14
An ECG traces the electrical activity of the heart.
Tolerability (adverse event reporting)
时间窗: Day 1 through 14 days post last dose
Adverse events reported
Pharmacokinetic Tmax of IkT-148009
时间窗: Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.
Time to reach maximum concentration (Tmax)
Safety: incidence of abnormal Clinical Laboratory Data
时间窗: Safety assessments performed from Day 1 through Day 14
Clinical chemistry tests will include albumin, alkaline phosphatase, total bilirubin, calcium, cholesterol, creatinine, creatinine clearance, creatinine kinase (CK), gamma-glutamyltransferase (γ-GT), glucose, lactate dehydrogenase (LDH), inorganic phosphorus, lipase, amylase, potassium, magnesium, total protein, aspartate transaminase (AST), alanine transaminase (ALT), sodium, triglycerides, urea and uric acid, bicarbonate and chloride. TSH levels will also be monitored. CBC assessments will include hemoglobin, hematocrit, red blood cell (RBC) count, reticulocyte count, white blood cells (WBC) count with differential, platelet count and PT-INR. PT-INR should be reported in both prothrombin time and international normalized ratio. Men and women will undergo additional laboratory tests for reproductive organ function to include leutenizing hormone (LH), follicle stimulating hormone (FSH), testosterone and inhibin B.
Safety: C-SSRS
时间窗: Safety assessments performed from Day 1 through Day 14
Columbia Suicide Severity Rating Scale questionaire
Pharmacokinetic AUC to last time point of IkT-148009
时间窗: Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.
Area under the concentration-time curve from time zero to last time point (AUC0-last)
Pharmacokinetic distribution half-life of IkT-148009
时间窗: Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.
The distributional half-life and terminal half-life (t1/2)
Pharmacokinetic exposure of IkT-148009 steady-state
时间窗: Part B, C: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192 hours post-dose.
Exposure (AUC SS)
Pharmacokinetic trough concentration of IkT-148009
时间窗: Part A: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post dose. Part B: As in Part A plus 120, 144, 168, 192 hours post-dose.
Exposure (Ctrough)
Pharmacokinetic concentration of IkT-148009 steady-state at maximum concentration
时间窗: Part B, C: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 192 hours post-dose.
Exposure (Cmax SS)
次要结局
未报告次要终点