A Phase 1, 6-part, Open-label, Fixed-sequence Study to Evaluate the Effects of Lithium, Valproic Acid, and Lamotrigine on the Single-dose Pharmacokinetics of KarXT and Effects of KarXT on the Single-dose Pharmacokinetics of Lithium, Valproic Acid, and Lamotrigine in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 133
- 试验地点
- 1
- 主要终点
- Maximum observed plasma concentration (Cmax)
研究概览
简要总结
The purpose of this study is to evaluate the effects of lithium, valproic acid, and lamotrigine on the single-dose pharmacokinetics (PK) of KarXT and the effect of KarXT on the single-dose PK of lithium, valproic acid, and lamotrigine in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- 是
入选标准
- •Healthy male and female [individual not of childbearing potential (INOCBP)] participants as determined by no clinically significant deviation from normal in medical history, physical examination, 12-lead ECG, vital signs, and clinical laboratory determinations.
- •BMI of 18.0 to 32.0 kg/m2, inclusive.
排除标准
- •History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, GI, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the participant or the validity of the study results. Note: Any grade of hepatic impairment (Child-Pugh Grade A or higher) is excluded.
- •Parts B and D only: History of pancreatitis.
- •Any significant acute or chronic medical illness, in the opinion of the investigator.
- •History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma or known history of prostate hypertrophy or nocturia.
- •Parts E & F only: history of skin rash and mucus ulcerations of no obvious cause and Gilbert's syndrome
- •Other protocol-defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Part A
干预措施: Xanomeline/Trospium Chloride (Drug)
Part A
干预措施: Lithium (Drug)
Part B
干预措施: Xanomeline/Trospium Chloride (Drug)
Part B
干预措施: Valproic Acid (Drug)
Part C
干预措施: Xanomeline/Trospium Chloride (Drug)
Part C
干预措施: Lithium (Drug)
Part D
干预措施: Xanomeline/Trospium Chloride (Drug)
Part D
干预措施: Valproic Acid (Drug)
Part E
干预措施: Xanomeline/Trospium Chloride (Drug)
Part E
干预措施: Lamotrigine (Drug)
Part F
干预措施: Xanomeline/Trospium Chloride (Drug)
Part F
干预措施: Lamotrigine (Drug)
结局指标
主要结局
Maximum observed plasma concentration (Cmax)
时间窗: Up to day 54
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T))
时间窗: Up to day 54
Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF))
时间窗: Up to day 54
次要结局
- Number of participants with adverse events (AEs)(Up to 28 days post discontinuation of dosing)
- Number of participants with serious adverse events (SAEs)(Up to 28 days post discontinuation of dosing)
- Number of participants with physical examination abnormalities(Up to 2 days post discontinuation of dosing)
- Number of participants with vital sign abnormalities(Up to 2 days post discontinuation of dosing)
- Number of participants with 12-lead electrocardiogram (ECG) abnormalities(Up to 2 days post discontinuation of dosing)
- Number of participants with clinical laboratory abnormalities(Up to 2 days post discontinuation of dosing)
- Columbia-Suicide Severity Rating Scale (C-SSRS)(Up to 2 days post discontinuation of dosing)
- Number of participants with AEs of Special Interest (AESIs)(Up to 28 days post discontinuation of dosing)