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A Study to Test the Pharmacodynamic, Pharmacokinetic, Safety, and Tolerability of Padsevonil in Healthy Study Participants Receiving Either Ethanol or Cannabidiol

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ClinicalTrials.gov Identifier: NCT04039919
Recruitment Status : Recruiting
First Posted : July 31, 2019
Last Update Posted : August 27, 2019
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma S.P.R.L. )

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).

Condition or disease Intervention/treatment Phase
Healthy Participants Drug: Padsevonil Drug: Placebo (PSL) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
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
Actual Study Start Date : July 17, 2019
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Arm Intervention/treatment
Experimental: Part A: Padsevonil and Ethanol
Subjects will be randomized to receive Padsevonil and Ethanol.
Drug: Padsevonil
Padsevonil will be administered in predefined dosages.

Placebo Comparator: Part A: Padsevonil and Ethanol-Placebo
Subjects will be randomized to receive Padsevonil and Ethanol-Placebo.
Drug: Padsevonil
Padsevonil will be administered in predefined dosages.

No Intervention: Part A: Ethanol and Ethanol-Placebo
Subjects will be randomized to receive Ethanol and Ethanol-Placebo.
No Intervention: Part A: Ethanol-Placebo and Ethanol
Subjects will be randomized to receive Ethanol and Ethanol-Placebo.
Experimental: Part B: Padsevonil and Cannabidiol
Subjects will be randomized to receive Padsevonil and Cannabidiol.
Drug: Padsevonil
Padsevonil will be administered in predefined dosages.

Placebo Comparator: Part B: Padsevonil-Placebo and Cannabidiol
Subjects will be randomized to receive Padsevonil-Placebo and Cannabidiol.
Drug: Placebo (PSL)
Placebo will be provided matching Padsevonil to maintain the blinding.




Primary Outcome Measures :
  1. Percentage of smooth pursuit eye movements during Part A during Period 1 (Day 1) [ Time Frame: Day 1 of Period 1 ]
    Smooth pursuit to assess eye movement coordination and attention to evaluate the ethanol effect. The average percentage of smooth pursuit for all stimulus frequencies will be used as a parameter.

  2. Percentage of smooth pursuit eye movements during Part A during Period 2 (Day 1) [ Time Frame: Day 1 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 will be used as a parameter.

  3. Percentage of smooth pursuit eye movements during Part A during Period 4 (Day 5) [ Time Frame: Day 5 of Period 4 ]
    Smooth pursuit to assess eye movement coordination and attention to evaluate the interaction between treatment with padsevonil (PSL) and ethanol. The average percentage of smooth pursuit for all stimulus frequencies will be used as a parameter.

  4. Percentage of smooth pursuit eye movements during Part A during Period 5 (Day 7) [ Time Frame: Day 7 of Period 5 ]
    Smooth pursuit to assess eye movement coordination and attention to evaluate the interaction between treatment with padsevonil (PSL) and ethanol. The average percentage of smooth pursuit for all stimulus frequencies will be used as a parameter.

  5. Cmax,ss for padsevonil during part B [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part B ]
    Cmax,ss: Maximum observed plasma concentration at steady state

  6. Cmax,ss for cannabidiol during Part B [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part B ]
    Cmax,ss: Maximum observed plasma concentration at steady state

  7. AUC0-tau for padsevonil during Part B [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part B ]
    AUC0-tau: Area Under the Curve over a dosing interval

  8. AUC0-tau for cannabidiol during Part B [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part B ]
    AUC0-tau: Area Under the Curve over a dosing interval


Secondary Outcome Measures :
  1. Ethanol dose over time during Part A [ Time Frame: From 30 minutes loading phase up to 5 hours ]
    Continuous infusion will begin with a 30 minute loading phase and will continue for 5 hours with adjustments during the infusion.

  2. Cmax,ss for padsevonil during part A [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part A ]
    Cmax,ss: Maximum observed plasma concentration at steady state

  3. AUC0-tau for padsevonil during Part A [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part A ]
    AUC0-tau: Area Under the Curve over a dosing interval

  4. T1/2 for padsevonil during Part B [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part B ]
    t1/2: Apparent terminal half-life

  5. T1/2 for cannabidiol during Part B [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part B ]
    t1/2: Apparent terminal half-life

  6. CLss/F for padsevonil during Part B [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part B ]
    CLss/F: Apparent total body clearance at steady state following extravascular administration

  7. CLss/F for cannabidiol during Part B [ Time Frame: Plasma samples will be taken predose up to 12 hours post dose during part B ]
    CLss/F: Apparent total body clearance at steady state following extravascular administration

  8. Percentage of smooth pursuit eye movements during Part B [ Time Frame: Assessments are conducted on: Screening, Treatment Period 2: Day -1 and Day 5; Treatment Period 3: Day -1 and Day 16; Treatment Period 4 and 5: Day 1 and Day 5 ]
    Smooth pursuit to assess eye movement coordination and attention to evaluate the cannabidol effect. The average percentage of smooth pursuit for all stimulus frequencies will be used as a parameter.

  9. Saccadic peak velocity to assess sedation during Part A [ Time Frame: Assessments are conducted on: Screening; Treatment Periods 1 and 2, Day 1; Treatment Period 4, Day 5; Treatment Period 5, Day 7 ]
    Sixteen saccades will be recorded with interstimulus intervals varying randomly. Average values of latency (reaction time), saccadic peak velocity of all correct saccades, and inaccuracy of all saccades will be used as parameters.

  10. Saccadic peak velocity to assess sedation during Part B [ Time Frame: Assessments are conducted on: Screening, Treatment Period 2: Day -1 and Day 5; Treatment Period 3: Day -1 and Day 16; Treatment Period 4 and 5: Day 1 and Day 5 ]
    Sixteen saccades will be recorded with interstimulus intervals varying randomly. Average values of latency (reaction time), saccadic peak velocity of all correct saccades, and inaccuracy of all saccades will be used as parameter

  11. Adaptive tracking to assess visuo-motor control and vigilance during Part A [ Time Frame: Assessments are conducted on: Screening; Treatment Periods 1 and 2, Day 1; Treatment Period 4, Day 5; Treatment Period 5, Day 7 ]
    The adaptive tracking test will be performed as originally described by Borland and Nicholson (Borland and Nicholson, 1984). Performance will be scored after a fixed period of 3.5 minutes and reflected visuo-motor control and vigilance. The average performance scores will be used in the analysis.

  12. Adaptive tracking to assess visuo-motor control and vigilance during Part B [ Time Frame: Assessments are conducted on: Screening, Treatment Period 2: Day -1 and Day 5; Treatment Period 3: Day -1 and Day 16; Treatment Period 4 and 5: Day 1 and Day 5 ]
    The adaptive tracking test will be performed as originally described by Borland and Nicholson (Borland and Nicholson, 1984). Performance will be scored after a fixed period of 3.5 minutes and reflected visuo-motor control and vigilance. The average performance scores will be used in the analysis.

  13. Body sway to assess postural stability during Part A [ Time Frame: Assessments are conducted on: Screening; Treatment Periods 1 and 2, Day 1; Treatment Period 4, Day 5; Treatment Period 5, Day 7 ]
    Body Sway test measures the study participant's body movements in a single direction. Study participants will be asked to stand erect and motionless with their eyes closed. The amplitude and direction of any Body Sway will be recorded for 1 minute.

  14. Body sway to assess postural stability during Part B [ Time Frame: Assessments are conducted on: Screening, Treatment Period 2: Day -1 and Day 5; Treatment Period 3: Day -1 and Day 16; Treatment Period 4 and 5: Day 1 and Day 5 ]
    Body Sway test measures the study participant's body movements in a single direction. Study participants will be asked to stand erect and motionless with their eyes closed. The amplitude and direction of any Body Sway will be recorded for 1 minute.

  15. Number of participants with Adverse events during Part A [ Time Frame: From Screening up to the safety follow up visit of part A on study Day 26 ]
    An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.

  16. Number of participants with Adverse events during Part B [ Time Frame: From Screening up to the safety follow up visit of part B on study Day 66 ]
    An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.

  17. Number of participants with Serious Adverse events during Part A [ Time Frame: From Baseline up to the safety follow up visit of part A on study Day 26 ]

    A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

    • Results in death
    • Is life-threatening
    • Requires in patient hospitalization or prolongation of existing hospitalization
    • Is a congenital anomaly or birth defect
    • Is an infection that requires treatment parenteral antibiotics
    • Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above

  18. Number of participants with Serious Adverse events during Part B [ Time Frame: From Baseline up to the safety follow up visit of part B on study Day 66 ]

    A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

    • Results in death
    • Is life-threatening
    • Requires in patient hospitalization or prolongation of existing hospitalization
    • Is a congenital anomaly or birth defect
    • Is an infection that requires treatment parenteral antibiotics
    • Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above

  19. Number of participants with Treatment-related Adverse events during Part A [ Time Frame: From Baseline up to the safety follow up visit of part A on study Day 26 ]
    Treatment-related Adverse events is an Adverse Event for which a causal relationship between the product and the occurrence is suspected.

  20. Number of participants with Treatment-related Adverse events during Part B [ Time Frame: From Baseline up to the safety follow up visit of part B on study Day 66 ]
    Treatment-related Adverse events is an Adverse Event for which a causal relationship between the product and the occurrence is suspected.

  21. Number of participants with Adverse events leading to discontinuation of the study during Part A [ Time Frame: From Baseline up to the safety follow up visit of part A on study Day 26 ]
    An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

  22. Number of participants with Adverse events leading to discontinuation of the study during Part B [ Time Frame: From Baseline up to the safety follow up visit of part B on study Day 66 ]
    An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04039919


Contacts
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Contact: UCB Cares +1844599 ext 2273 UCBCares@ucb.com

Locations
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Netherlands
Up0071 001 Recruiting
Leiden, Netherlands
Sponsors and Collaborators
UCB Biopharma S.P.R.L.
Investigators
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Study Director: UCB Cares 001 844 599 2273 (UCB)

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Responsible Party: UCB Biopharma S.P.R.L.
ClinicalTrials.gov Identifier: NCT04039919     History of Changes
Other Study ID Numbers: UP0071
2019-000703-32 ( EudraCT Number )
First Posted: July 31, 2019    Key Record Dates
Last Update Posted: August 27, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Due to the small sample size in this trial, Individual Patient Data cannot be adequately anonymized and there is a reasonable likelihood that individual participants could be re-identified. For this reason, data from this trial cannot be shared.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):
Ethanol
Cannabidiol
Padsevonil
Additional relevant MeSH terms:
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Ethanol
Epidiolex
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Anticonvulsants