A Phase 1, Randomized, Placebo-controlled Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Emraclidine Following Multiple Ascending Oral Doses in Healthy Elderly Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 52
- 试验地点
- 10
- 主要终点
- Apparent Volume of Distribution DuringTerminal Phase (Vz/F) of Emraclidine
研究概览
简要总结
This study is to assess how oral emraclidine moves through the body of healthy elderly adult participants, and assess adverse events, and tolerability.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 85 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI is ≥ 18.0 to ≤ 32.0 kg/m2 after rounding to the tenths decimal at Screening. BMI is calculated as weight in kg divided by the square of height measured in meters.
- •Body weight > 45 kg at the time of screening and upon initial confinement.
- •A condition of general good health, based upon the results of a medical history, physical examination, vital signs, laboratory profile and a 12-lead ECG.
排除标准
- •History of any clinically significant cardiac, respiratory (except mild asthma as a child), renal, hepatic, gastrointestinal, genitourinary, immunological, hematologic, neurological or psychiatric disease or disorder, or any other uncontrolled medical illness.
- •History of any clinically significant sensitivity or allergy to any medication or food.
- •Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than successfully treated non-metastatic cutaneous squamous cell, basal cell carcinoma or localized carcinoma in situ of the cervix.
研究组 & 干预措施
Emraclidine or Placebo- Group 3
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days.
干预措施: Placebo (Drug)
Emraclidine or Placebo- Group 4
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days.
干预措施: Emraclidine (Drug)
Emraclidine or Placebo- Group 4
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days.
干预措施: Placebo (Drug)
Emraclidine or Placebo- Group 1
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days
干预措施: Emraclidine (Drug)
Emraclidine or Placebo- Group 1
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days
干预措施: Placebo (Drug)
Emraclidine or Placebo- Group 2
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days
干预措施: Emraclidine (Drug)
Emraclidine or Placebo- Group 2
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days
干预措施: Placebo (Drug)
Emraclidine or Placebo- Group 3
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days.
干预措施: Emraclidine (Drug)
Emraclidine or Placebo- Group 5
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days.
干预措施: Emraclidine (Drug)
Emraclidine or Placebo- Group 5
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days.
干预措施: Placebo (Drug)
Emraclidine or Placebo- Group 6
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days.
干预措施: Placebo (Drug)
Emraclidine or Placebo- Group 6
Participants will receive oral doses of emraclidine or placebo for 10 days or 17 days.
干预措施: Emraclidine (Drug)
结局指标
主要结局
Apparent Volume of Distribution DuringTerminal Phase (Vz/F) of Emraclidine
时间窗: Up to approximately 20 days
Vz/F of Emraclidine
Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
AUCtau of Metabolite (CV-0000364)
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS)
时间窗: Up to approximately 20 days
AIMS assesses abnormal involuntary movements, such as tardive dyskinesia, associated with antipsychotic drugs; it measures facial, oral, extremities, and trunk movements, as well as the participant's awareness of abnormal movements. The first 10 items are rated on a none (0) to severe (4) scale. There are an additional 2 items on dental status that are answered yes or no.
Change From Baseline in Barnes Akathisia Rating Scale (BARS)
时间窗: Up to approximately 20 days
BARS is a 4-item rating scale used to assess drug-induced akathisia. The scale comprises items for rating the observable restless movements that characterize the condition, the subjective awareness of restlessness, and any distress associated with the akathisia (each on a 4-point scale from normal \[0\] to severe \[3\]). In addition, there is a global severity for akathisia rated on a 6-point scale (absent \[0\] to severe akathisia \[5\]).
Change From Baseline in Simpson-Angus Scale (SAS)
时间窗: Up to approximately 20 days
SAS is a 10-item rating scale for assessment of antipsychotic-induced parkinsonism in both clinical practice and research settings. Each item ranges from 0 (normal) to 4 (extreme symptoms). The scale consists of 1 item measuring gait (hypokinesia), 6 items measuring rigidity, and 3 items measuring glabella tap, tremor, and salivation, respectively.
Maximum Observed Plasma Concentration (Cmax) of Emraclidine
时间窗: Up to approximately 20 days
Cmax of Emraclidine
Maximum Observed Plasma Concentration (Cmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
Cmax of Metabolite (CV-0000364)
Time to Cmax (Tmax) of Emraclidine
时间窗: Up to approximately 20 days
Tmax of Emraclidine
Time to Cmax (Tmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
Tmax of Metabolite (CV-000036)
Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) of Emraclidine
时间窗: Up to approximately 20 days
AUCt of Emraclidine
Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) Metabolite (CV-000036)
时间窗: Up to approximately 20 days
AUCt of Metabolite (CV-000036)
Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Emraclidine
时间窗: Up to approximately 20 days
AUCtau of Emraclidine
Minimum plasma concentration (Cmin) of Emraclidine
时间窗: Up to approximately 20 days
Cmin of Emraclidine
Average plasma concentration (Cavg) of Emraclidine
时间窗: Up to approximately 20 days
Cavg of Emraclidine
Metabolite to Parent Ratio (MRCmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
MRCmax of Metabolite (CV-0000364) calculated from Cmax
Metabolite to Parent Ratio (MRAUCtau) of Emraclidine
时间窗: Up to approximately 20 days
MRAUCtau of Emraclidine based on AUCtau
Metabolite to Parent Ratio (MRAUCtau) of Metabolite (CV-000036)
时间窗: Up to approximately 20 days
MRAUCtau of Metabolite (CV-000036) based on AUCtau
Terminal Phase Elimination Half-Life (t1/2) of Emraclidine
时间窗: Up to approximately 20 days
Terminal phase elimination half-life of Emraclidine
Terminal Phase Elimination Half-Life (t1/2) of Metabolite (CV-000036)
时间窗: Up to approximately 20 days
Terminal phase elimination half-life of Metabolite (CV-000036)
Apparent terminal phase elimination constant (β) of Emraclidine
时间窗: Up to approximately 20 days
β of Emraclidine
Accumulation ratio for Cmax (RacCmax) of Emraclidine
时间窗: Up to approximately 20 days
RacCmax of Emraclidine
Accumulation ratio for Cmax (RacCmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
RacCmax of Metabolite (CV-0000364)
Accumulation ratio for AUCtau (RacAUCtau) of Emraclidine
时间窗: Up to approximately 20 days
RacAUCtau of Emraclidine
Accumulation ratio for AUCtau (RacAUCtau) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
RacAUCtau of Metabolite (CV-0000364)
Apparent Clearance of Drug from Plasma (CL/F) of Emraclidine
时间窗: Up to approximately 20 days
CL/F of Emraclidine
Number of Participants Experiencing Adverse Events
时间窗: Up to approximately 50 days
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Number of Participants with Clinical Significant Change From Baseline in Vital Sign Measurements
时间窗: Up to approximately 20 days
Number of participants with clinical significant change from baseline in vital sign measurements like systolic and diastolic blood pressure will be assessed.
Number of Participants with Clinical Significant Change from Baseline in Electrocardiogram (ECG)
时间窗: Up to approximately 20 days
12-lead resting ECG will be recorded.
Number of Participants with Clinical Significant Change in Physical Examinations
时间窗: Up to approximately 20 days
Number of participants with clinical significant change in physical examinations will be assessed.
Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to approximately 20 days
The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior.
Time to Cmax (Tmax) of Emraclidine
时间窗: Up to approximately 20 days
Tmax of Emraclidine
Time to Cmax (Tmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
Tmax of Metabolite (CV-000036)
Apparent Volume of Distribution DuringTerminal Phase (Vz/F) of Emraclidine
时间窗: Up to approximately 20 days
Vz/F of Emraclidine
Maximum Observed Plasma Concentration (Cmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
Cmax of Metabolite (CV-0000364)
Number of Participants Experiencing Adverse Events
时间窗: Up to approximately 50 days
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Number of Participants with Clinical Significant Change From Baseline in Vital Sign Measurements
时间窗: Up to approximately 20 days
Number of participants with clinical significant change from baseline in vital sign measurements like systolic and diastolic blood pressure will be assessed.
Number of Participants with Clinical Significant Change from Baseline in Electrocardiogram (ECG)
时间窗: Up to approximately 20 days
12-lead resting ECG will be recorded.
Number of Participants with Clinical Significant Change in Physical Examinations
时间窗: Up to approximately 20 days
Number of participants with clinical significant change in physical examinations will be assessed.
Number of Participants with Clinical Significant Change in Clinical Laboratory Test Results Like Hematology will be Assessed
时间窗: Up to approximately 20 days
Number of participants with clinical significant change in clinical laboratory test results will be assessed.
Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to approximately 20 days
The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS)
时间窗: Up to approximately 20 days
AIMS assesses abnormal involuntary movements, such as tardive dyskinesia, associated with antipsychotic drugs; it measures facial, oral, extremities, and trunk movements, as well as the participant's awareness of abnormal movements. The first 10 items are rated on a none (0) to severe (4) scale. There are an additional 2 items on dental status that are answered yes or no.
Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
AUCtau of Metabolite (CV-0000364)
Change From Baseline in Barnes Akathisia Rating Scale (BARS)
时间窗: Up to approximately 20 days
BARS is a 4-item rating scale used to assess drug-induced akathisia. The scale comprises items for rating the observable restless movements that characterize the condition, the subjective awareness of restlessness, and any distress associated with the akathisia (each on a 4-point scale from normal \[0\] to severe \[3\]). In addition, there is a global severity for akathisia rated on a 6-point scale (absent \[0\] to severe akathisia \[5\]).
Change From Baseline in Simpson-Angus Scale (SAS)
时间窗: Up to approximately 20 days
SAS is a 10-item rating scale for assessment of antipsychotic-induced parkinsonism in both clinical practice and research settings. Each item ranges from 0 (normal) to 4 (extreme symptoms). The scale consists of 1 item measuring gait (hypokinesia), 6 items measuring rigidity, and 3 items measuring glabella tap, tremor, and salivation, respectively.
Maximum Observed Plasma Concentration (Cmax) of Emraclidine
时间窗: Up to approximately 20 days
Cmax of Emraclidine
Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) of Emraclidine
时间窗: Up to approximately 20 days
AUCt of Emraclidine
Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) Metabolite (CV-000036)
时间窗: Up to approximately 20 days
AUCt of Metabolite (CV-000036)
Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Emraclidine
时间窗: Up to approximately 20 days
AUCtau of Emraclidine
Minimum plasma concentration (Cmin) of Emraclidine
时间窗: Up to approximately 20 days
Cmin of Emraclidine
Minimum plasma concentration (Cmin) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
Cmin of Metabolite (CV-0000364)
Average plasma concentration (Cavg) of Emraclidine
时间窗: Up to approximately 20 days
Cavg of Emraclidine
Average plasma concentration (Cavg) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
Cavg of Metabolite (CV-0000364)
Metabolite to Parent Ratio (MRCmax) of Emraclidine
时间窗: Up to approximately 20 days
MRCmax of Emraclidine calculated from Cmax
Metabolite to Parent Ratio (MRCmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
MRCmax of Metabolite (CV-0000364) calculated from Cmax
Metabolite to Parent Ratio (MRAUCtau) of Emraclidine
时间窗: Up to approximately 20 days
MRAUCtau of Emraclidine based on AUCtau
Metabolite to Parent Ratio (MRAUCtau) of Metabolite (CV-000036)
时间窗: Up to approximately 20 days
MRAUCtau of Metabolite (CV-000036) based on AUCtau
Terminal Phase Elimination Half-Life (t1/2) of Emraclidine
时间窗: Up to approximately 20 days
Terminal phase elimination half-life of Emraclidine
Terminal Phase Elimination Half-Life (t1/2) of Metabolite (CV-000036)
时间窗: Up to approximately 20 days
Terminal phase elimination half-life of Metabolite (CV-000036)
Apparent terminal phase elimination constant (β) of Emraclidine
时间窗: Up to approximately 20 days
β of Emraclidine
Apparent terminal phase elimination constant (β) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
β of Metabolite (CV-0000364)
Peak-to-trough ratio (PTR) of Emraclidine
时间窗: Up to approximately 20 days
PTR of Emraclidine
Peak-to-trough ratio (PTR) of Metabolite (CV-000036)
时间窗: Up to approximately 20 days
PTR of Metabolite (CV-000036)
Accumulation ratio for Cmax (RacCmax) of Emraclidine
时间窗: Up to approximately 20 days
RacCmax of Emraclidine
Accumulation ratio for Cmax (RacCmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
RacCmax of Metabolite (CV-0000364)
Accumulation ratio for AUCtau (RacAUCtau) of Emraclidine
时间窗: Up to approximately 20 days
RacAUCtau of Emraclidine
Accumulation ratio for AUCtau (RacAUCtau) of Metabolite (CV-0000364)
时间窗: Up to approximately 20 days
RacAUCtau of Metabolite (CV-0000364)
Apparent Clearance of Drug from Plasma (CL/F) of Emraclidine
时间窗: Up to approximately 20 days
CL/F of Emraclidine
次要结局
未报告次要终点