A Phase 1, Open-label Trial to Evaluate the Pharmacokinetics of CVL-231 Following Single Oral Administration of Modified- and Immediate-release Formulations Under Fasted and Fed Conditions in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Primary Part A & B: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (CV-0000364)
研究概览
简要总结
A 2-part, crossover design, open-label treatment trial with 4 periods, 4 sequences (Part A) to evaluate MR formulations of CVL-231 and a 2 periods, 2 sequences (Part B) to understand effect of food on CVL-231 exposures from an MR formulation.
详细描述
CVL-231 is a muscarinic acetylcholine receptor (mAChR) activator that selectively binds to the M4 muscarinic receptor subtype (M4 mAChR) and is being developed for treatment of psychosis in schizophrenia. Part A of this 2-part trial will investigate the PK of CVL-231 in healthy participants following a single oral dose of CVL-231 as 3 modified-release (MR) formulations with different release rates and an immediate-release (IR) formulation under fasted conditions. Upon selection of an MR formulation with appropriate PK characteristics, the effect of food on the PK of CVL-231 and its metabolite following single oral doses of the selected MR formulation may be evaluated in Part B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Women of nonchildbearing potential and men 18 to 55 years, inclusive.
- •Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator.
- •Body mass index of 18.5 to 30.0 kg/m2 and a total body weight >50 kg (110 lbs).
- •Sexually active men with a pregnant or a nonpregnant partner of childbearing potential must agree to comply with protocol contraception requirements during treatment and through 7 days post dose. In addition, male participants should not donate sperm for a minimum of 7 days following the last dose of IMP.
- •Capable of giving signed informed consent.
- •Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements.
排除标准
- •Current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, endocrine, hematological, immunological, or neurological disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.
- •Current or past personal or family history of any psychiatric disorder as classified by DSM-5 criteria.
- •Epilepsy or a history of seizures except for a single seizure episode, eg, a childhood febrile seizure, a seizure related to trauma or alcohol withdrawal, or an unexplained loss of consciousness.
- •History of moderate to severe substance or alcohol-use disorder (excluding caffeine) within 12 months prior to signing the ICF.
- •Serious risk of suicide in the opinion of the investigator
- •Receipt of SARS-CoV2 vaccine or booster within 28 days of dosing with CVL-231, or plan to receive SARS-CoV2 vaccination or booster from Screening through 5 days after last dose of CVL-
- •Have recently been diagnosed with symptomatic COVID-19 or test positive for COVID-19 within 30 days prior to signing the ICF.
- •Either of the following:
- •History of HIV, hepatitis B, or hepatitis C infection
- •Positive result for HIV antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody
- •Positive drug screen for illicit drugs or a positive test for alcohol
- •12-lead ECG demonstrating pre-defined abnormalities at Screening and Day -1 based on local evaluation.
- •Abnormal clinical laboratory tests or vital sign measurements at the Screening Visit and at Day -1 (check-in) for each period
- •Known to be allergic or hypersensitive to the IMP or any of its components.
- •Participation in any clinical trial within 90 days prior to signing the ICF.
研究组 & 干预措施
Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
Oral Dose
干预措施: 10 mg CVL-231 as IR formulation (Drug)
Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
Oral Dose
干预措施: 30 mg CVL-231 as slow-release MR formulation (Drug)
Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
Oral Dose
干预措施: 30 mg CVL-231 as medium release MR formulation (Drug)
Part A: Single doses of CVL-231 IR/MR formulations in healthy participants under fasted conditions
Oral Dose
干预措施: 30 mg CVL-231 as fast release MR formulation (Drug)
Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions
Oral Dose
干预措施: 30 mg CVL-231 Target Release, Fasted (Drug)
Part B: Single doses of CVL-231 target release formulation under fasted and fed conditions
Oral Dose
干预措施: 30 mg CVL-231 Target Release, Fed (Drug)
结局指标
主要结局
Primary Part A & B: Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (CV-0000364)
时间窗: Up to 72 Hours in each period
Primary Part A & B: Time to Maximum Concentration (Tmax) for CVL-231 and Metabolite (CV-0000364)
时间窗: Up to 72 Hours in each period
Primary Part A & B: Time prior to the first measurable (non-zero) concentration (Tlag) for CVL-231 and Metabolite (CV-0000364)
时间窗: Up to 72 Hours in each period
Primary Part A & B: Area under the plasma concentration-time curve from time 0 to the last measurable time point (AUClast) for CVL-231 and Metabolite (CV-0000364)
时间窗: Up to 72 Hours in each period
Primary Part A & B: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for CVL-231 and Metabolite (CV-0000364)
时间窗: Up to 72 Hours in each period
Primary Part A & B: Elimination half-life (t½) for CVL-231 and Metabolite (CV-0000364)
时间窗: Up to 72 Hours in each period
Primary Part A only: Dose normalized Cmax, derived by Cmax divided by the dose administered (Cmax/D) for CVL-231 and Metabolite (CV-0000364)
时间窗: Up to 72 Hours in each period
Primary Part A only: Dose normalized AUClast, derived by AUClast divided by the dose administered (AUClast/D) for CVL-231 and Metabolite (CV-0000364)
时间窗: Up to 72 Hours in each period
Primary Part A only: Dose normalized AUCinf, derived by AUCinf divided by the dose administered (AUCinf/D) for CVL-231 and Metabolite (CV-0000364)
时间窗: Up to 72 Hours in each period
次要结局
- Secondary: Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)(Up to Day 14)
- Secondary: Incidence of clinically significant changes in electrocardiogram (ECG) results(Up to 72 Hours in each period)
- Secondary: Incidence of clinically significant changes in clinical laboratory results(Up to 72 Hours in each period)
- Secondary: Incidence of clinically significant changes in vital sign measurements(Up to 72 Hours in each period)
- Secondary: Incidence of clinically significant changes in physical and neurological examination results(Up to 72 Hours in each period)
- Secondary: Clinically significant findings in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS)(Up to 72 Hours in each period)