Clinical trial NCT04039919: A Study to Test the Pharmacodynamic, Pharmacokinetic, Safety, and Tolerability of Padsevonil in Healthy Study Participants Receiving Either Ethanol or Cannabidiol
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Ethanol
Cannabidiol
Padsevonil
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2019-07-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Smooth Pursuit Eye Movements on Day 1 of Period 1 or Day 3 of Period 2 During Part A
timeFrame: 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
measure: Percentage of Smooth Pursuit Eye Movements on Day 5 of Period 4 or Day 7 of Period 5 During Part A
timeFrame: 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
measure: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part B
timeFrame: Predose up to 12 hours postdose
measure: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Cannabidiol During Part B
timeFrame: Predose up to 12 hours postdose
measure: Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part B
timeFrame: Predose up to 12 hours post dose
measure: Area Under the Curve Over a Dosing Interval (AUCtau) of Cannabidiol During Part B
timeFrame: Predose up to 12 hours postdose
Secondary outcomes:
measure: Breath Concentration of Ethanol Over Time on Day 1 of Period 1 or Day 3 of Period 2 During Part A
timeFrame: -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
measure: Breath Concentration of Ethanol Over Time on Day 5 of Period 4 or Day 7 of Period 5 During Part A
timeFrame: -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
measure: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Padsevonil During Part A
timeFrame: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose on Day 5
measure: Area Under the Curve Over a Dosing Interval (AUCtau) of Padsevonil During Part A
timeFrame: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose on Day 5
measure: Half-life (t1/2) of Padsevonil During Part B
timeFrame: Predose up to 12 hours postdose
measure: Half-life (t1/2) of Cannabidiol During Part B
timeFrame: Predose up to 12 hours postdose
measure: Apparent Total Body Clearance at Steady State (CLss/F) of Padsevonil During Part B
timeFrame: Predose up to 12 hours postdose
measure: Apparent Total Body Clearance at Steady State (CLss/F) of Cannabidiol During Part B
timeFrame: Predose up to 12 hours postdose
measure: Percentage of Smooth Pursuit Eye Movements During Part B
timeFrame: Treatment Period 1: Screening, Day 1 and Day 2
measure: Saccadic Peak Velocity to Assess Sedation on Day 1 of Period 1 or Day 3 of Period 2 During Part A
timeFrame: 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
measure: Saccadic Peak Velocity to Assess Sedation on Day 5 of Period 4 or Day 7 of Period 5 During Part A
timeFrame: 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
measure: Saccadic Peak Velocity to Assess Sedation During Part B
timeFrame: Treatment Period 1: Screening, Day 1 and Day 2
measure: Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 1 of Period 1 or Day 3 of Period 2 During Part A
timeFrame: 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
measure: Adaptive Tracking to Assess Visuo-Motor Control and Vigilance on Day 5 of Period 4 or Day 7 of Period 5 During Part A
timeFrame: 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
measure: Adaptive Tracking to Assess Visuo-Motor Control and Vigilance During Part B
timeFrame: Treatment Period 1: Screening, Day 1 and Day 2
measure: Body Sway to Assess Postural Stability on Day 1 of Period 1 or Day 3 of Period 2 During Part A
timeFrame: 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
measure: Body Sway to Assess Postural Stability on Day 5 of Period 4 or Day 7 of Period 5 During Part A
timeFrame: 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
measure: Body Sway to Assess Postural Stability During Part B
timeFrame: Treatment Period 1: Screening, Day 1 and Day 2
measure: Number of Participants With Adverse Events During Part A
timeFrame: From Screening up to the Safety Follow-up visit of Part A (up to Day 26)
measure: Number of Participants With Adverse Events During Part B
timeFrame: From Screening up to the Safety Follow-up visit of Part B (up to Day 66)
measure: Number of Participants With Serious Adverse Events During Part A
timeFrame: From Screening up to the Safety Follow-up visit of Part A (up to Day 26)
measure: Number of Participants With Serious Adverse Events During Part B
timeFrame: From Screening up to the Safety Follow-up visit of Part B (up to Day 66)
measure: Number of Participants With Treatment-related Adverse Events During Part A
timeFrame: From Baseline up to Safety Follow-up visit of Part A (up to Day 26)
measure: Number of Participants With Treatment-related Adverse Events During Part B
timeFrame: From Baseline up to Safety Follow-up visit of Part B (up to Day 66)
measure: Number of Participants With Adverse Events Leading to Discontinuation of the Study During Part A
timeFrame: From Screening up to Safety Follow-up visit of Part A (up to Day 26)
measure: Number of Participants With Adverse Events Leading to Discontinuation of the Study During Part B
timeFrame: From Screening up to Safety Follow-up visit of Part B (up to Day 66)
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Up0071 001
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: