A Double-Blind, Placebo-Controlled, Randomized, Single-Center, Cross-Over Study to Investigate the Pharmacodynamic, Pharmacokinetic, Safety, and Tolerability Profiles of Padsevonil in Healthy Study Participants Receiving Either Ethanol or Cannabidiol
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Area Under the Curve Over a Dosing Interval (AUCtau) of Cannabidiol During Part B
研究概览
简要总结
The purpose of the study is to evaluate the pharmacodynamic (PD) interaction between steady-steady treatment with padsevonil (PSL) and Ethanol and the pharmacokinetic (PK) interaction between stead-state treatment with PSL and cannabidiol (CBD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
- •Participant must have previous experience with alcohol consumption and, therefore, must be familiar with the effects and able to tolerate social amounts of alcohol
- •Participant has a body weight of at least 50 kg (males) or 45 kg (females) and body mass index (BMI) within the range 18 to 30 kg/m2 (inclusive)
- •Participants are male or female:
- •A male participant must agree to use contraception as detailed in the protocol during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period
- •A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
- •Not a woman of childbearing potential (WOCBP) as defined n the protocol OR
- •A WOCBP who agrees to follow the contraceptive guidance in the protocol during the Treatment Period and for at least 90 days after the last dose of study treatment
排除标准
- •Participant has history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data
- •Participant has a history of chronic alcohol or drug abuse within the previous 6 months or the presence of drug or alcohol dependency at Screening or Day -1 or tests positive for alcohol and/or drugs at Screening or Day -1
- •Participant has a known hypersensitivity to any components of the study medication or comparative drugs (and/or an investigational device) as stated in this protocol
- •Participant has a history of unexplained syncope or a family history of sudden death due to long QT syndrome
- •Participant has lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
- •Participant has past or intended use of over-the-counter or prescription medication including herbal medications within 2 weeks or 5 half-lives prior to dosing
- •Participant has used hepatic enzyme-inducing drugs within 2 months prior to dosing
- •Participant has alanine transaminase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) >1.0x upper limit of normal (ULN)
- •Participant has current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •Participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline
- •Participant has the presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to dosing
- •Participant has a positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention
- •Participant has a positive human immunodeficiency virus (HIV) antibody test
研究组 & 干预措施
Part A: Padsevonil and Ethanol
Subjects will be randomized to receive Padsevonil and Ethanol.
干预措施: Padsevonil (Drug)
Part A: Padsevonil and Ethanol-Placebo
Subjects will be randomized to receive Padsevonil and Ethanol-Placebo.
干预措施: Padsevonil (Drug)
Part B: Padsevonil and Cannabidiol
Subjects will be randomized to receive Padsevonil and Cannabidiol.
干预措施: Padsevonil (Drug)
Part B: Padsevonil-Placebo and Cannabidiol
Subjects will be randomized to receive Padsevonil-Placebo and Cannabidiol.
干预措施: Placebo (PSL) (Drug)
结局指标
主要结局
Area Under the Curve Over a Dosing Interval (AUCtau) of Cannabidiol During Part B
时间窗: Predose up to 12 hours postdose
AUCtau is the area under the curve over a dosing interval of CBD.
Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part B
时间窗: Predose up to 12 hours post dose
AUCtau is the area under the curve over a dosing interval of padsevonil.
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Cannabidiol During Part B
时间窗: Predose up to 12 hours postdose
Cmax is maximum observed plasma concentration at steady state of CBD.
Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A
时间窗: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2
Smooth pursuit to assess eye movement coordination and attention to evaluate the ethanol effect. The average percentage of smooth pursuit for all stimulus frequencies was used as a parameter. Participants received either ethanol or placebo on Day 1 of Period 1 or on Day 3 of Period 2. Therefore, the results were summarized by treatment.
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part B
时间窗: Predose up to 12 hours postdose
Cmax is maximum observed plasma concentration at steady state of padsevonil.
Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A
时间窗: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 5 of Period 4 or Day 7 of Period 5
Smooth pursuit to assess eye movement coordination and attention to evaluate the ethanol effect. The average percentage of smooth pursuit for all stimulus frequencies was used as a parameter. Participants received either ethanol or placebo on Day 5 of Period 4 or Day 7 of Period 5. Therefore, the results were summarized by treatment.
次要结局
- Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part A(Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose on Day 5)
- Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A(-0.4, -0.3, -0.2, -0.16, -0.08, Predose, 0.16, 0.3, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7 and 8 hours postdose on Day 5 of Period 4 or Day 7 of Period 5)
- Body Sway to Assess Postural Stability During Part B(Treatment Period 1: Screening, Day 1 and Day 2)
- Apparent Total Body Clearance at Steady State (CLss/F) of Padsevonil During Part B(Predose up to 12 hours postdose)
- Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A(-0.4, -0.3, -0.2, -0.16, -0.08, Predose, 0.16, 0.3, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7 and 8 hours postdose on Day 1 of Period 1 or on Day 3 of Period 2)
- Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part A(Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose on Day 5)
- Half-life (t1/2) of Padsevonil During Part B(Predose up to 12 hours postdose)
- Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A(Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 5 of Period 4 or Day 7 of Period 5)
- Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A(Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours on Day 5 of Period 4 or Day 7 of Period 5)
- Number of Participants With Serious Adverse Events During Part A(From Screening up to the Safety Follow-up visit of Part A (up to Day 26))
- Half-life (t1/2) of Cannabidiol During Part B(Predose up to 12 hours postdose)
- Saccadic Peak Velocity to Assess Sedation During Part B(Treatment Period 1: Screening, Day 1 and Day 2)
- Adaptive Tracking to Assess Visuo-Motor Control and Vigilance During Part B(Treatment Period 1: Screening, Day 1 and Day 2)
- Number of Participants With Adverse Events During Part B(From Screening up to the Safety Follow-up visit of Part B (up to Day 66))
- Number of Participants With Treatment-related Adverse Events During Part B(From Baseline up to Safety Follow-up visit of Part B (up to Day 66))
- Number of Participants With Adverse Events Leading to Discontinuation of the Study During Part B(From Screening up to Safety Follow-up visit of Part B (up to Day 66))
- Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A(Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2)
- Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A(Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2)
- Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A(Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours postdose on Day 1 of Period 1 or Day 3 of Period 2)
- Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A(Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10 hours on Day 5 of Period 4 or Day 7 of Period 5)
- Number of Participants With Adverse Events During Part A(From Screening up to the Safety Follow-up visit of Part A (up to Day 26))
- Number of Participants With Serious Adverse Events During Part B(From Screening up to the Safety Follow-up visit of Part B (up to Day 66))
- Number of Participants With Treatment-related Adverse Events During Part A(From Baseline up to Safety Follow-up visit of Part A (up to Day 26))
- Apparent Total Body Clearance at Steady State (CLss/F) of Cannabidiol During Part B(Predose up to 12 hours postdose)
- Percentage of Smooth Pursuit Eye Movements During Part B(Treatment Period 1: Screening, Day 1 and Day 2)
- Number of Participants With Adverse Events Leading to Discontinuation of the Study During Part A(From Screening up to Safety Follow-up visit of Part A (up to Day 26))