A Phase 2 Study Evaluating the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of KM-819 in Healthy Older Adults and Participants with Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 314
- 试验地点
- 3
- 主要终点
- Part 1a,1b and 2: Number of participants with adverse events and serious adverse events
研究概览
简要总结
The goal of this study is to test KM-819 in halting or slowing the progression of Parkinson's disease.
The study evaluates the safety and tolerability of multiple ascending doses of KM-819 in healthy older adults and participants with Parkinson's disease.
详细描述
The overall study will consist of three parts (Part 1a, Part 1b and Part 2).
Part 1 of this study will evaluate the safety, tolerability and plasma PK of multiple ascending doses (MAD) of KM-819 in healthy older adults (Part 1a) and participants with Parkinson's disease (Part 1b).
- Part 1a is a randomized, double-blind, Multiple Ascending Dose (MAD) study in healthy older adults that will include 3 cohorts.
- Part 1b is a randomized, double-blind, MAD study in participants with Parkinson's disease that will include 3 cohorts.
Part 2 of the study is a randomized, double-blind, multiple dose study in participants with Parkinson's disease that will include 2 cohorts. It is designed to test the safety, tolerability, plasma PK and pharmacodynamic effects of KM-819 in participants with Parkinson's disease. The study will also assess the degree to which those treated with KM-819 will experience gains in overall daily function within the context of improved Parkinson's disease motor and non-motor symptoms in comparison to placebo. Participants will be randomized to receive KM-819 or matching placebo at doses to be determined based on the findings from Part 1 in a 2:1 ratio.
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
Double-Blinded
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant is a healthy volunteer or has a clinical diagnosis of idiopathic Parkinson's disease.
- •Participant is on a stable dose of medications to treat Parkinson's disease at least 8 weeks prior to randomization
- •Presence of idiopathic Parkinson's disease Hoehn and Yahr Stage ≤ 4
- •History or current use of dopamine/dopaminergic drugs, levodopa with decarboxylase inhibitor or dopaminergic agonists, with a stable dosage for at least 30 days prior to Screening
- •Body mass index (BMI) within the range 18.5 to 35 kg/m2 (inclusive)
- •A male participant must not have a pregnant or breastfeeding partner and must agree to use a highly effective contraception method starting from Screening and refrain from donating sperm during this period
- •A female participant is eligible to participate if she is not pregnant, not breastfeeding
排除标准
- •Diagnosis of neurodegenerative disorder other than idiopathic Parkinson's disease resulting in dementia or atypical parkinsonism
- •Life-time history of a suicide attempt as determined by the Columbia-Suicide Severity Rating Scale (C-SSRS) for the Screening
- •Evidence of cognitive decline defined by the Montreal Cognitive Assessment (MoCA) score ≤25 for healthy normal population (Part 1a) and ≤21 for the patient population (Part 1b and Part 2)
- •History of levodopa-induced motor fluctuations or dyskinesia
- •Prior surgical treatment for Parkinson's disease
- •Clinically significant brain abnormalities on or contraindication to a structural magnetic resonance imaging (MRI)
- •Significant respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, pancreatic, musculoskeletal, genitourinary, immunological or dermatological disorders.
研究组 & 干预措施
Part 1a: Cohort 1.1a Dose 400 mg
Healthy older adult participants will receive oral 400 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: KM-819 (Drug)
Part 1a: Cohort 1.1a Dose 400 mg
Healthy older adult participants will receive oral 400 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: Placebo (Drug)
Part 1a: Cohort 1.2a Dose 600 mg
Healthy older adult participants will receive oral 600 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: KM-819 (Drug)
Part 1a: Cohort 1.2a Dose 600 mg
Healthy older adult participants will receive oral 600 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: Placebo (Drug)
Part 1a: Cohort 1.3a Dose 800 mg
Healthy older adult participants will receive oral 800 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: KM-819 (Drug)
Part 1a: Cohort 1.3a Dose 800 mg
Healthy older adult participants will receive oral 800 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: Placebo (Drug)
Part 1b: Cohort 1.1b Dose 200 mg
Participants with Parkinson's disease will receive oral 200 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: KM-819 (Drug)
Part 1b: Cohort 1.1b Dose 200 mg
Participants with Parkinson's disease will receive oral 200 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: Placebo (Drug)
Part 1b: Cohort 1.2b Dose 400 mg
Participants with Parkinson's disease will receive oral 400 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: KM-819 (Drug)
Part 1b: Cohort 1.2b Dose 400 mg
Participants with Parkinson's disease will receive oral 400 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: Placebo (Drug)
Part 1b: Cohort 1.3b Dose 600 mg
Participants with Parkinson's disease will receive oral 600 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: KM-819 (Drug)
Part 1b: Cohort 1.3b Dose 600 mg
Participants with Parkinson's disease will receive oral 600 mg dose of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to administration of study intervention and will be required to fast for 1 hour after administration of study intervention.
干预措施: Placebo (Drug)
Part 2: Cohort 2.1 Dose X
Participants with Parkinson's disease will receive oral doses of KM-819 (dose to be determined based on the findings from Part 1) or matching placebo once-daily for 730 days and will be allowed to take study intervention with or without fasting.
干预措施: KM-819 (Drug)
Part 2: Cohort 2.1 Dose X
Participants with Parkinson's disease will receive oral doses of KM-819 (dose to be determined based on the findings from Part 1) or matching placebo once-daily for 730 days and will be allowed to take study intervention with or without fasting.
干预措施: Placebo (Drug)
Part 2: Cohort 2.2 Dose Y
Participants with Parkinson's disease will receive oral doses of KM-819 (dose to be determined based on the findings from Part 1) or matching placebo once-daily for 730 days and will be allowed to take study intervention with or without fasting.
干预措施: KM-819 (Drug)
Part 2: Cohort 2.2 Dose Y
Participants with Parkinson's disease will receive oral doses of KM-819 (dose to be determined based on the findings from Part 1) or matching placebo once-daily for 730 days and will be allowed to take study intervention with or without fasting.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1a,1b and 2: Number of participants with adverse events and serious adverse events
时间窗: Part 1a and Part 1b: From screening (Day -42 to -3) up to 7 days and Part 2: From screening (Day -42 to -2) to 730 days
To evaluate the safety and tolerability of multiple ascending doses of KM-819
Part 2: Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II: Activities of Daily Living (ADL) Score at Day 730
时间窗: From screening (Day -42 to -2) to Day 730
Activities of Daily living (ADL) will be assessed via MDS-UPDRS score. MDS-UPDRS Part II is a self-administered questionnaire that assesses the motor experience of daily living in participants with Parkinson's disease. Score: 0: Normal, 1: Slight, 2: Mild, 3: Moderate, 4: Severe. Higher the score, the more severe the condition or symptom
次要结局
- Part 1a and 1b: Maximum concentration (Cmax)(Day 1)
- Part 1a and 1b: Time to achieve Cmax (tmax)(Day 1)
- Part 1a and 1b: Area under the concentration-time curve (AUC) from pre-dose (time zero) to the time of the last quantifiable concentration AUC(0-t)(Day 1)
- Part 1a and 1b: Minimum concentration (Cmin)(Day 1)
- Part 1a and 1b: AUC normalized to dose administered (AUC_D)(Day 1)
- Part 1a and 1b: Percentage of AUCinf that is extrapolated beyond the time of the last quantifiable concentration [%AUC (extrap)](Day 1)
- Part 1a and 1b: AUC from pre-dose (time zero) to 24 hours post-dose [AUC(0-24)](Day 1)
- Part 1a and 1b: Cmax normalized to dose administered (Cmax_D)(Day 1)
- Part 1a and 1b: AUC from pre-dose (time zero) extrapolated to time infinity [AUC(0-inf)](Day 1)
- Part 1a and 1b: Apparent terminal elimination half-life (t½)(Day 1)
- Part 1a and 1b: Terminal elimination rate constant (λz)(Day 1)
- Part 1a and 1b: Apparent oral clearance (CL/F)(Day 1)
- Part 1a and 1b: AUC(0-t) at steady state (Vz/F)(Day 1)
- Part 1a and 1b: AUC(0-t) at steady state [AUC(0-t_ss)](Day 7)
- Part 1a and 1b: AUCtau at steady state [AUC(tau_ss)](Day 7)
- Part 1a and 1b: Cmax at steady state (Cmax,ss)(Day 7)
- Part 1a and 1b: tmax at steady state (tmax,ss)(Day 7)
- Part 1a and 1b: Ctrough at steady state (Ctrough_ss)(Day 7)
- Part 1a and 1b: Minimum concentration at steady state (Cmin,ss)(Day 7)
- Part 1a and 1b: Average observed concentration at steady state (Cav,ss)(Day 7)
- Part 1a and 1b: Accumulation ratio calculated using AUC [Rac (AUC)](Day 7)
- Part 1a and 1b: Accumulation ratio calculated using Cmax [Rac (Cmax)](Day 7)
- Part 1a and 1b: Apparent oral clearance at steady state (CL/Fss)(Day 7)
- Part 1a and 1b: AUC normalized to dose administered at steady state (AUCss_D)(Day 7)
- Part 1a and 1b: Cmax_ss normalized to dose administered (Cmaxss_D)(Day 7)
- Part 1a and 1b: Fraction of dose excreted in urine (Fe)(Day 7)
- Part 1a and 1b: Renal clearance (CLR)(Day 7)
- Part 2: Sparse plasma PK blood sampling for population PK analysis(Day 1, Day 7, Day 30 and Day 180)