A Phase 1, Open-Label Trial to Assess the Absorption, Metabolism, Excretion, and Mass Balance of [14C]-Darigabat Following a Single Oral Dose in Healthy Adult Male Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- AUC from Time 0 to the Time of the Last Measured Concentration (AUClast) of Darigabat
研究概览
简要总结
The primary purpose of this trial is to determine the mass balance, routes, and rates of elimination of total radioactivity and characterize the pharmacokinetics (PK) of darigabat, and total radioactivity in plasma and whole blood following administration of a single oral dose of [14C]-darigabat in healthy adult male 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
- Male
- 接受健康志愿者
- 是
入选标准
- •Body mass index of 18.5 to 35.0 kilograms per square meters (kg/m^2), inclusive, and a total body weight ≥50 kg [110 Pounds (lbs)] at Screening.
- •A male participant who is sexually active with a pregnant or a nonpregnant partner of childbearing potential must agree to use a condom during the trial and for 93 days after the dose of investigational medicinal product (IMP). In addition, male participants should not donate sperm for a minimum of 93 days following the dose of IMP.
- •Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures.
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 Columbia-Suicide Severity Rating Scale (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) Serious risk of suicide in the opinion of the investigator is also exclusionary.
- •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.
- •Positive result for human immunodeficiency viruses (HIV) antibody, hepatitis B surface antigen, hepatitis B total core antibody, or hepatitis C antibody with detectable viral Ribonucleic acid (RNA) levels at Screening. Note: Positive or indeterminate test result for hepatitis C antibody should follow with hepatitis C virus polymerase chain reaction (PCR) RNA test. If result is positive, the participant is excluded.
- •Positive drug screen [including cotinine and Tetrahydrocannabinol (THC)] or a positive test for alcohol.
- •Known allergy or hypersensitivity to the IMP, closely related compounds, or any of their specified ingredients.
- •NOTE: Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Darigabat
Participants will receive a single oral dose of darigabat.
干预措施: [14C]-darigabat (Drug)
结局指标
主要结局
AUC from Time 0 to the Time of the Last Measured Concentration (AUClast) of Darigabat
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Maximum Observed Plasma Concentration (Cmax) of Darigabat
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Apparent Total Clearance After Oral Administration (CL/F) of Darigabat
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Amount Excreted in Urine (Aeu) of Total Radioactivity
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Urine PK parameters will be assessed.
Terminal Phase Half-life (t½) of Darigabat
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Ratio of Plasma AUCinf for Darigabat to Total Radioactivity
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Time to Maximum Observed Concentration (Tmax) of Darigabat
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Area Under the Concentration Time Curve (AUC) from Time Zero to Infinity (AUCinf) of Darigabat
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Time to Last Quantifiable (Tlast) Concentration of Darigabat
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Darigabat
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Ratio of Whole Blood AUCinf for Total Radioactivity to Plasma Total Radioactivity
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Amount Excreted in Feces (Aef) of Total Radioactivity
时间窗: Pre-dose and at multiple time points post-dose up to Day 15
Fecal PK parameters will be assessed.
次要结局
- Structural Elucidation of [14C]-darigabat Metabolites ≥10% of the Total [14C]-darigabat Radioactivity Found in Plasma, Urine and Feces(Pre-dose and at multiple time points post-dose up to Day 15)
- Number of Participants with Clinically Significant Changes in Vital Signs(Up to Day 15)
- Metabolite Profile of [14C]-darigabat in Plasma, Urine and Feces(Pre-dose and at multiple time points post-dose up to Day 15)
- Identification of [14C]-darigabat Metabolites Found in Plasma, Urine and Feces(Pre-dose and at multiple time points post-dose up to Day 15)
- Number of Participants with Adverse Events (AEs)(Up to Day 16)
- Number of Participants with Clinically Significant Changes in Laboratory Assessments(Up to Day 15)
- Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values(Up to Day 15)
- Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results(Up to Day 15)