A Phase 1, Open-Label, Fixed Sequence, Drug-Drug Interaction Study to Evaluate the Effect of Inhibition of Uridine 5'-Diphosphate-glucuronosyltransferases (UGTs) on the Pharmacokinetics of Ecopipam Tablets and Its Active Metabolite (EBS-101-40853) in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Cmax of ecopipam in the presence of mefenamic acid
研究概览
简要总结
This is a single center, open-label, fixed sequence, drug-drug interaction (DDI) study in healthy subjects.
详细描述
Following a 28-day Screening period, eligible subjects will enter the clinical research unit (CRU) and will be enrolled into either Cohort A or B. Subjects in both cohorts will receive a single dose of ecopipam on Day 1. On Day 7, subjects will begin taking a UGT inhibitor according to their assigned cohort. Subjects in Cohort A will receive mefenamic acid 250 mg every 6 hours for 7 days, while subjects in Cohort B will receive divalproex sodium ER 1250 mg once a day for 10 days. A single oral dose of ecopipam will also be administered to Cohort A on Day 7, 1 hour after the first dose of mefenamic acid, and to Cohort B on Day 10, 1 hour after administration of divalproex sodium ER. Subjects in Cohort A will continue taking mefenamic acid through the evening of Day 13 and will remain in the CRU until discharged on Day 14/ET. Subjects in Cohort B will continue taking divalproex sodium ER through Day 16 and will remain in the CRU until discharge on Day 17/ET.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Male subjects or female subjects of non-childbearing potential
- •≥18 and ≤55 years of age at the time of consent
- •BMI >18.5 and <30 kg/m2 and a weight of ≥50 kg
- •Sexually active males must use a double barrier method of contraception during the study and for at least 90 days after the last dose of study drug
- •Male subjects must be willing not to donate sperm until 90 days following the last study drug administration
排除标准
- •Personal or family History of significant medical illness
- •Clinically significant abnormalities on screening tests/exams
- •History of or significant risk of committing suicide
- •Donation of plasma within 7 days prior to dosing
- •Donation or significant loss of blood within 30 days prior to the first dosing
- •Major surgery within 3 months or minor surgery within 1 month prior to admission
- •Use of prohibited prescription, over-the-counter medications or natural health products
- •Alcohol-based products 24 hours prior to admission
- •Female subjects who are currently pregnant or lactating
- •Use of tobacco or nicotine products within 3 months prior to Screening
- •Significant alcohol consumption
- •History of drug abuse within the previous 2 years, or a positive drug screen
- •History of allergy to study medications
- •Not suitable for study in the opinion of the Principal Investigator
研究组 & 干预措施
Cohort A
Ecopipam HCL - 2 doses of 200mg
Mefenamic acid 250mg Q6H for 7 days
干预措施: ecopipam HCL (Drug)
Cohort A
Ecopipam HCL - 2 doses of 200mg
Mefenamic acid 250mg Q6H for 7 days
干预措施: Mefenamic acid (Drug)
Cohort B
Ecopipam HCL - 2 doses of 200mg
Divalproex acid 1250mg QD for 10 days
干预措施: ecopipam HCL (Drug)
Cohort B
Ecopipam HCL - 2 doses of 200mg
Divalproex acid 1250mg QD for 10 days
干预措施: Divalproex Sodium ER (Drug)
结局指标
主要结局
Cmax of ecopipam in the presence of mefenamic acid
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of ecopipam in the presence of divalproex sodium ER
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of ecopipam in the absence of mefenamic acid
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Cmax of ecopipam in the absence of divalproex sodium ER
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of ecopipam in the presence of mefenamic acid
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of ecopipam in the absence of mefenamic acid
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of ecopipam in the presence of divalproex sodium ER
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUCinf of ecopipam in the absence of divalproex sodium ER
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-143 of ecopipam in the presence of mefenamic acid
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-143 of ecopipam in the absence of mefenamic acid
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-143 of ecopipam in the presence of divalproex sodium ER
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
AUC0-143 of ecopipam in the absence of divalproex sodium ER
时间窗: Up to Day 16
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
次要结局
- Tmax of mefenamic acid(Up to Day 16)
- AUCtau of mefenamic acid(Up to Day 16)
- Cmax of VPA(Up to Day 16)
- Tmax of VPA(Up to Day 16)
- AUCtau of VPA(Up to Day 16)
- AUCinf of EBS-101-40853(Up to Day 16)
- Absolute values of neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)(Up to Day 17)
- Absolute values of Red blood cell (RBC) count (M/uL)(Up to Day 17)
- Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK)(Up to Day 17)
- Absolute values of urine glucose(Up to Day 17)
- Absolute values of urine blood(Up to Day 17)
- AUC0-143 of EBS-101-40853(Up to Day 16)
- Safety and tolerability as demonstrated by concomitant medications(Up to Day 42)
- AEs with relatedness associated with mefenamic acid(Up to Day 42)
- Absolute values of hematocrit (%)(Up to Day 17)
- Absolute values of albumin and total protein (g/dL)(Up to Day 17)
- Absolute values of urine specific gravity(Up to Day 17)
- Absolute values of urine pH(Up to Day 17)
- Cmax of EBS-101-40853(Up to Day 16)
- Cmax of mefenamic acid(Up to Day 16)
- t½ of mefenamic acid(Up to Day 16)
- Safety and tolerability as demonstrated by MOAA/S(Up to Day 17)
- AEs with relatedness associated with divalproex sodium ER(Up to Day 42)
- AEs with relatedness associated with ecopipam(Up to Day 42)
- Change from Day -1 to Day of Discharge in creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)(Up to Day 17)
- Change from Day -1 to Day of Discharge in urine protein(Up to Day 17)
- Change from Day -1 to Day of Discharge in albumin and total protein (g/dL)(Up to Day 17)
- Change from Day -1 to Day of Discharge in urine specific gravity(Up to Day 17)
- Change from Day -1 to Day of Discharge in urine pH(Up to Day 17)
- Change from Day -1 to Day of Discharge in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK) (U/L)(Up to Day 17)
- Change from Day -1 to Day of Discharge in urine blood(Up to Day 17)
- Change from Day -1 to Day of Discharge in urine bilirubin, urobilinogen, and nitrite (Milligrams per deciliter)(Up to Day 17)
- Change from Day -1 to Day of Discharge in urine leukocytes by dipstick(Up to Day 17)
- Change from Day -1 to Day of Discharge in urine glucose(Up to Day 17)
- Change from Day -1 to Day of Discharge in urine ketones(Up to Day 17)
- Change from pre-dose for the respective day in ECG parameters: PR, QRS, QT, and QTcF (Milliseconds)(Up to Day 10)
- Change from pre-dose for the respective day in oral temperature (degrees Celsius)(Up to Day 17)
- Safety and tolerability as demonstrated by C-SSRS(Up to Day 17)
- Absolute values of white blood cell (WBC) count (K/Ul)(Up to Day 17)
- Absolute values of platelets (K/uL)(Up to Day 17)
- Absolute values of hemoglobin (g/dL)(Up to Day 17)
- Absolute values of urine ketones(Up to Day 17)
- Change from Day -1 to Day of Discharge in platelets (K/uL)(Up to Day 17)
- Change from pre-dose for the respective day in heart rate (beats/minute)(Up to Day 17)
- Absolute values of blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)(Up to Day 17)
- Absolute values of creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)(Up to Day 17)
- Absolute values of urine protein(Up to Day 17)
- Absolute values of urine bilirubin, urobilinogen, and nitrite(Up to Day 17)
- Change from Day -1 to Day of Discharge in hematocrit (%)(Up to Day 17)
- Change from Day -1 to Day of Discharge in hemoglobin (g/dL)(Up to Day 17)
- Absolute values of electrocardiogram (ECG) parameters: PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) (Milliseconds)(Up to Day 10)
- Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHG)(Up to Day 17)
- Change from pre-dose for the respective day in SBP and DBP (mmHG)(Up to Day 17)
- Change from Day 6 to Day of Discharge in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (U/L)(Up to Day 17)
- Absolute values of oral temperature (degrees Celsius)(Up to Day 17)
- Absolute values of heart rate (beats/minute)(Up to Day 17)
- Absolute values of respiratory rate (breaths/minute)(Up to Day 17)
- Change from pre-dose for the respective day in respiratory rate (breaths/minute)(Up to Day 17)
- Absolute values of urine leukocytes by dipstick(Up to Day 17)
- Change from Day -1 to Day of Discharge in white blood cell (WBC) count (K/Ul)(Up to Day 17)
- Change from Day -1 to Day of Discharge in neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)(Up to Day 17)
- Change from Day -1 to Day of Discharge in Red blood cell (RBC) count (M/uL)(Up to Day 17)
- Change from Day -1 to Day of Discharge in blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)(Up to Day 17)