An Adaptive Two-part Randomized, Double Blind, Placebo-controlled Phase 2 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of Emraclidine in Participants With Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 268
- 试验地点
- 12
- 主要终点
- Part A Only-Peak-to-trough ratio (PTR) of Metabolite (CV-0000364)
研究概览
简要总结
Schizophrenia is a common and severe psychiatric illness characterized by extreme disturbances of cognition and thought, affecting language, perception and sense of self. This study will assess adverse events, change in disease activity, and how oral emraclidine moves through the body in adult participants with schizophrenia
Emraclidine is an investigational drug being developed for the treatment of schizophrenia. Participants are placed in one of two parts, Part A or Part B, where each group will receive a different treatment. Participants will receive either oral emraclidine or placebo. Approximately 268 participants will be enrolled across roughly 32 sites in the United States.
Participants in Part A will be assigned to oral emraclidine or placebo administered for 14 days or up to 21 days depending on cohort. Cohorts without titration include a 14-day treatment period at target dose. Cohorts with titration are comprised of a titration period of up to 7 days and a 14-day treatment period at the cohort target dose. Participants in Part B will receive oral emraclidine or placebo. Participants will be followed for 30 days after the last dose of the study drug.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI within 18 to 40 kg/m2 (inclusive of both values), and body weight > 50 kg (110 lbs).
- •(Part A only): Positive and Negative Syndrome Scale (PANSS) total score < 80 at Screening and at Baseline
- •(Part B only): Participant experiencing an acute exacerbation of psychotic symptoms with onset less than 2 months prior to Screening
- •(Part B only): Participant must have a PANSS total score from 80 to 120, inclusive, at Screening and at Baseline
- •(Part B only): Participant MUST have a score of ≥ 4 (moderate or greater) for ≥ 2 of the following PANSS Positive Scale items at Screening and at Baseline
- •(Part B only): Participant must have a Clinical Global Impression of Severity (CGIS) score ≥ 4 (at least moderately ill) at Screening and Baseline
排除标准
- •Any primary DSM-5 disorder other than schizophrenia (current nicotine use disorder and caffeine use disorder are allowed) within 12 months before Screening.
- •History of clozapine exposure.
- •History of treatment resistance to schizophrenia medications, defined as failure to respond to 2 or more adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) within the last 12 months
研究组 & 干预措施
Placebo-Part A
Participants will be assigned to receive one of multiple ascending doses of oral placebo for 14 or up to 21 days, followed by a 30-day safety follow-up period.
干预措施: Placebo (Drug)
Emraclidine-Part B
Participants will receive oral emraclidine for 42 days followed by a 30-day safety follow-up period.
干预措施: Emraclidine (Drug)
Emraclidine Part A
Participants will be assigned to receive one of multiple ascending doses of oral emraclidine for 14 or up to 21 days, followed by a 30-day safety follow-up period.
干预措施: Emraclidine (Drug)
Placebo-Part B
Participants will receive placebo for 42 days followed by a 30-day safety follow-up period.
干预措施: Placebo (Drug)
结局指标
主要结局
Part A Only-Peak-to-trough ratio (PTR) of Metabolite (CV-0000364)
时间窗: Up to approximately 21 days
PTR of Metabolite (CV-0000364)
Part A Only-Accumulation ratio for AUCtau (RacAUCtau) of Emraclidine
时间窗: Up to approximately 21 days
RacAUCtau of Emraclidine
Part A Only-Metabolite to Parent Ratio (MRCmax) of Metabolite (CV-0000364) calculated from Cmax
时间窗: Up to approximately 21 days
MRCmax of Metabolite (CV-000036)
Part A Only- Metabolite to Parent Ratio (MRAUCtau) of Metabolite (CV-0000364)
时间窗: Up to approximately 21 days
MRAUCtau of Metabolite (CV-0000364)
Part A Only- Terminal Phase Elimination Half-Life (t1/2) of of Metabolite (CV-0000364)
时间窗: Up to approximately 21 days
Terminal phase elimination half-life of Metabolite (CV-0000364)
Part A Only-Terminal elimination rate constant (λz) of Metabolite (CV-0000364)
时间窗: Up to approximately 21 days
λz of Metabolite (CV-0000364)
Part B Only-Maximum Observed Plasma Concentration (Cmax) of Emraclidine
时间窗: Up to approximately 24 days
Cmax of Emraclidine
Part B Only-Time to Cmax (Tmax) of Emraclidine
时间窗: Up to approximately 24 days
Tmax of Emraclidine
Part B Only-Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) of Emraclidine
时间窗: Up to approximately 24 days
AUCt of Emraclidine
Part B Only-Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Emraclidine
时间窗: Up to approximately 24 days
AUCtau of Emraclidine
Number of Participants with Adverse Events (AEs)
时间窗: Up to approximately 74 days
An adverse event (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. The investigator assesses the relationship of each event to the use of study.
Part A Only-Maximum Observed Plasma Concentration (Cmax) of Emraclidine
时间窗: Up to approximately 24 days
Cmax of Emraclidine
Part A Only-Time to Cmax (Tmax) of Emraclidine
时间窗: Up to approximately 24 days
Tmax of Emraclidine
Part A Only-Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) of Emraclidine
时间窗: Up to approximately 24 days
AUCt of Emraclidine
Part A Only-Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Emraclidine
时间窗: Up to approximately 24 days
AUCtau of Emraclidine
Part A Only-Maximum metabolite concentration (MRCmax) of Emraclidine
时间窗: Up to approximately 21 days
MRCmax of Emraclidine
Part A Only- Area under the metabolite concentration-time curve over the dosing interval (MRAUCtau) of Emraclidine
时间窗: Up to approximately 21 days
MRAUCtau of Emraclidine
Part A Only- Minimum plasma concentration (Cmin) of Emraclidine
时间窗: Up to approximately 21 days
Cmin of Emraclidine
Part A Only-Average plasma concentration (Cavg) of Emraclidine
时间窗: Up to approximately 21 days
Cavg of Emraclidine
Part A Only- Terminal Phase Elimination Half-Life (t1/2) of Emraclidine
时间窗: Up to approximately 21 days
Terminal phase elimination half-life of Emraclidine
Part A Only-Terminal elimination rate constant (λz) of Emraclidine
时间窗: Up to approximately 21 days
λz of Emraclidine
Part A Only-Apparent Clearance of Drug from Plasma (CL/F) of Emraclidine
时间窗: Up to approximately 21 days
CL/F of Emraclidine
Part A Only-Apparent Volume of Distribution DuringTerminal Phase (Vz/F) of Emraclidine
时间窗: Up to approximately 21 days
Vz/F of Emraclidine
Part A Only-Time to Cmax (Tmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 24 days
Tmax of Metabolite (CV-0000364)
Part A Only-Peak-to-trough ratio (PTR) of Emraclidine
时间窗: Up to approximately 21 days
PTR of Emraclidine
Part A Only- Accumulation ratio for Cmax (RacCmax) of Emraclidine
时间窗: Up to approximately 21 days
RacCmax of Emraclidine
Part A Only-Accumulation ratio for AUCta (RacAUCtau) of Emraclidine
时间窗: Up to approximately 21 days
RacAUCta of Emraclidine
Part A Only-Maximum Observed Plasma Concentration (Cmax) of Metabolite (CV-0000364)
时间窗: Up to approximately 24 days
Cmax of Metabolite (CV-0000364)
Part A Only-Area under the plasma concentration-time curve over the dosing interval (AUCtau) of Metabolite (CV-000036)
时间窗: Up to approximately 24 days
AUCtau of Metabolite (CV-000036)
Part A Only-Area Under the Concentration-Time Curve from Time 0 to Time t (AUCt) Metabolite (CV-000036)
时间窗: Up to approximately 24 days
AUCt of Metabolite (CV-000036)
Part A Only-Maximum metabolite concentration (MRCmax) of Metabolite (CV-000036)
时间窗: Up to approximately 21 days
MRCmax of Metabolite (CV-000036)
Part A Only- Area under the metabolite concentration-time curve over the dosing interval (MRAUCtau) of Metabolite (CV-000036)
时间窗: Up to approximately 21 days
MRAUCtau of Metabolite (CV-000036)
Part B Only-Change from Baseline in Positive and Negative Syndrome Scale (PANSS) total score
时间窗: Up to approximately week 6
PANSS is a 30-item clinician-reported rating scale which assesses both the positive and negative symptom syndromes of patients with schizophrenia. The PANSS consists of 3 subscales containing a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms.
次要结局
- Part B Only-Change from Baseline in in Clinical Global Impression of Severity (CGIS) score(Up to approximately 53 days)
- Part B Only-Change from Baseline in Positive and Negative Syndrome Scale (PANSS) total score(Up to approximately 74 days)
- Part B Only-Number of Participants achieving ≥ 30% improvement in PANSS total score(Up to approximately week 6)
- Part B Only-Number of Participants achieving remission (PANSS total score ≤ 60)(Up to approximately week 6)
- Part B Only-Change from Baseline in in Clinical Global Impression of Severity (CGIS) score(Up to approximately Week 6)