A Phase 1, Open-Label, Fixed-Sequence Trial to Evaluate the Effect of Esomeprazole and Gastric pH-Altering on the Pharmacokinetics of Emraclidine in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-t) of Emraclidine
研究概览
简要总结
The primary purpose of this study is to evaluate the potential of gastric pH-dependent drug-drug interaction effect of esomeprazole, a proton pump inhibitor (PPI), on the pharmacokinetics (PK) of emraclidine in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Sexually active women of childbearing potential must agree to use at least a highly effective birth control method, during the trial and for 7 days after the last dose of investigational medicinal product (IMP).
- •Body mass index of 18.5 to 35.0 kilogram per meter square (kg/m2), inclusive, and a total body weight ≥50 kg (110 [pounds] lbs).
- •Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECGs, vital sign measurements, and laboratory test results, as evaluated by the investigator.
排除标准
- •Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus, thyroid disorders), malignancy, hematological, immunological, neurological, or psychiatric disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.
- •"Yes" responses for any of the following items on the C-SSRS (within the individual's lifetime):
- •Suicidal Ideation Item 3 (Active Suicidal Ideation with Any Methods [Not Plan] without Intent to Act)
- •Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan)
- •Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent)
- •Any of the Suicidal Behavior items (Actual Attempt, Interrupted Attempt, Aborted Attempt, Preparatory Acts or Behavior)
- •"Yes" responses for any of the following items on the C-SSRS (within past 12 months):
- •Suicidal Ideation Item 1 (Wish to be Dead)
- •Suicidal Ideation Item 2 (Non-Specific Active Suicidal Thoughts)
- •Any condition or surgery that could possibly affect drug absorption, including, but not limited to, bowel resections, bariatric weight loss surgery/procedures, gastrectomy, and cholecystectomy.
- •Use of any prescription and over-the-counter medications from 28 days prior to first dose of IMP or likely to require concomitant therapy. Vaccinations or boosters within 28 days of planned dosing or while on trial are prohibited.
- •Positive result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis B total core antibody, or hepatitis C antibody with detectable viral ribonucleic acid (RNA) levels at Screening.
- •Positive drug screen (including cotinine and tetrahydrocannabinol [THC]) or a positive test for alcohol.
- •Any of the following clinical laboratory test results at the Screening Visit or Check-in (Day -1), which can be confirmed by a single repeat measurement, if deemed necessary:
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2× upper limit of normal (ULN).
- •Total bilirubin >1.5×ULN. If Gilbert's syndrome is suspected, total bilirubin >1.5×ULN is acceptable if the conjugated or direct bilirubin fraction is <20% of total bilirubin.
- •Known allergy or hypersensitivity to the IMP, closely related compounds, or any of their specified ingredients.
- •Female participants who are pregnant, breastfeeding, or planning to become pregnant during IMP treatment or within 7 days after the last dose of IMP. Women of childbearing potential must have a negative serum pregnancy test result at the Screening Visit and a negative urine pregnancy test result at Check-in.
- •Received IMP in a clinical trial of emraclidine.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Emraclidine 30 mg + Esomeprazole 40 mg
Participants will receive a single oral dose of 30 milligrams (mg) emraclidine on Day 1 of Treatment Period 1. After 6 days following the single dose of emraclidine in Treatment Period 1, participants will receive 40 mg esomeprazole, orally, once daily (QD) on Days 1 to 5 of Treatment Period 2. On Day 6 of Period 2, participants will receive 40 mg esomeprazole followed by a single oral dose of 30 mg emraclidine.
干预措施: Emraclidine (Drug)
Emraclidine 30 mg + Esomeprazole 40 mg
Participants will receive a single oral dose of 30 milligrams (mg) emraclidine on Day 1 of Treatment Period 1. After 6 days following the single dose of emraclidine in Treatment Period 1, participants will receive 40 mg esomeprazole, orally, once daily (QD) on Days 1 to 5 of Treatment Period 2. On Day 6 of Period 2, participants will receive 40 mg esomeprazole followed by a single oral dose of 30 mg emraclidine.
干预措施: Esomeprazole (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-t) of Emraclidine
时间窗: Pre-dose and at multiple time points post-dose on Days 1 to 6 in Period 1 and Days 6 to 11 in Period 2
Maximum Observed Plasma Concentration (Cmax) of Emraclidine
时间窗: Pre-dose and at multiple time points post-dose on Days 1 to 6 in Period 1 and Days 6 to 11 in Period 2
Time to Maximum (Peak) Plasma Concentration (Tmax) of Emraclidine
时间窗: Pre-dose and at multiple time points post-dose on Days 1 to 6 in Period 1 and Days 6 to 11 in Period 2
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Emraclidine
时间窗: Pre-dose and at multiple time points post-dose on Days 1 to 6 in Period 1 and Days 6 to 11 in Period 2
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to 29 days)
- Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)(Up to 45 days)
- Number of Participants With Clinically Significant Changes in Vital Sign Parameters(Up to 45 days)
- Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values(Up to 45 days)
- Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments(Up to 45 days)
- Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results(Up to 45 days)