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A Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal or Moderately Impaired Hepatic Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04136444
Recruitment Status : Suspended (Study recruitment temporarily halted as a precautionary measure due to the COVID-19 pandemic)
First Posted : October 23, 2019
Last Update Posted : April 21, 2020
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 plasma pharmacokinetic (PK), safety and tolerability of padsevonil (PSL) in hepatically impaired and non-hepatically impaired study participants.

Condition or disease Intervention/treatment Phase
Healthy Study Participants Impaired Hepatic Function Drug: Padsevonil Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: An Open-Label, Parallel-Group, Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal Hepatic Function or With Moderately Impaired Hepatic Function (Child-Pugh Class B)
Actual Study Start Date : October 28, 2019
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Arm Intervention/treatment
Experimental: Healthy participants
Participants will receive assigned single and multiple doses of padsevonil.
Drug: Padsevonil
Padsevonil will be administered in predefined dosages.
Other Names:
  • PSL
  • UCB0942

Experimental: Hepatically impaired participants
Participants will receive assigned single and multiple doses of padsevonil.
Drug: Padsevonil
Padsevonil will be administered in predefined dosages.
Other Names:
  • PSL
  • UCB0942




Primary Outcome Measures :
  1. The maximum plasma concentration (Cmax) of a single dose padsevonil (PSL) [ Time Frame: Plasma samples will be taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose ]
    Cmax: Maximum observed plasma concentration

  2. The area under the curve from 0 to t (AUC0-t) of a single dose padsevonil (PSL) [ Time Frame: Plasma samples will be taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose ]
    AUC0-t: Area under the plasma concentration-time curve from time zero to time t

  3. The area under the curve (AUC) of a single dose padsevonil (PSL) [ Time Frame: Plasma samples will be taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose ]
    AUC: Area under the plasma concentration-time curve from time 0 to infinity

  4. The maximum plasma concentration (Cmax,ss) of multiple doses padsevonil (PSL) [ Time Frame: On Days 8, 9, 10 and 11 PK samples will be taken predose. On Day 12, PK samples will be taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96 hours postdose ]
    Cmax,ss: Maximum observed plasma concentration at steady-state

  5. The area under the curve (AUCtau) over a dosing interval of multiple doses padsevonil (PSL) [ Time Frame: On Days 8, 9, 10 and 11 PK samples will be taken predose. On Day 12, PK samples will be taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96 hours postdose ]
    AUCtau: Area Under the Curve over a dosing interval


Secondary Outcome Measures :
  1. Number of participants with treatment-emergent adverse events (TEAEs) [ Time Frame: From Baseline until End of Study Visit (up to Day 18) ]
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event is characterized according to the intake of the study medication.

  2. Number of participants with serious adverse events (SAEs) [ Time Frame: From Baseline until End of Study Visit (up to Day 18) ]

    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

  3. Number of participants with treatment-emergent adverse events (TEAEs) leading to discontinuation of the study [ Time Frame: From Baseline until End of Study Visit (up to Day 18) ]
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event is characterized according to the intake of the study medication. TEAEs leading to discontinuation of the study are reported.



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 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participant must be male or female 18 to 70 years of age, inclusive, at the time of signing the informed consent
  • Participant must have body weight of at least 50 kg (males) or 45 kg (females) and body mass index within the range 18 to 38 kg/m^2 (inclusive)
  • Participants must meet the following requirements to be included in the study:

    1. A male participant must agree to use contraception during both Treatment Periods and for at least 7 days after the last dose of study medication and refrain from donating sperm during this period
    2. 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) OR A WOCBP who agrees to follow the contraceptive guidance during both Treatment Periods and for at least 90 days (or 5 terminal half-lives) after the final dose of study medication

      Specific inclusion criteria for study participants WITH moderate hepatic insufficiency:

  • Participant must have characteristics that will meet the clinical criteria usually found in participants with chronic hepatic insufficiency, as determined by medical history and physical examinations (eg, echography, scintigraphy, biopsy, or some specific laboratory values as evidence)

Exclusion Criteria:

  • Participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or compromise the study participant's ability to participate in this study, such as a history of schizophrenia, or other psychotic disorder, bipolar disorder, or severe unipolar depression. The presence of potential psychiatric exclusion criteria will be determined based on the psychiatric history collected at Screening Visit
  • Participant has a known hypersensitivity to any components of the study medication as stated in this protocol
  • Participant has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has had suicidal ideation in the past 6 months
  • Participant has past or intended use of over-the-counter or prescription medication including herbal remedies and hepatic enzyme inhibitors within 2 weeks or 5 half-lives prior to dosing, particularly for participants with hepatic impairment where t1/2 may be prolonged. Specific medications may be allowed. Participant has used hepatic enzyme-inducing drugs (eg, glucocorticoids, phenobarbital, phenytoin, isoniazid, or rifampicin, etc.) within 2 months prior to dosing unless required to treat an adverse event (AE). This does not include oral contraceptives not exceeding 30 μg ethinyl estradiol or postmenopausal hormone replacement therapy (HRT) or implants, patches, or intrauterine devices (IUDs) /intrauterine systems (IUSs) delivering progesterone (for female study participants) or acetaminophen with a maximal dose of 2 g/day or with a maximum of 10g over 15 days. In case of uncertainty, the UCB Study Physician should be consulted
  • Participant has a history of chronic alcohol or drug abuse within the previous 12 months. Participant has a positive pre-study drug/alcohol screen (to include at minimum: amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines). A participant with a positive finding on the drug screen may still be enrolled at the discretion of the Investigator if a plausible clinical explanation exists (eg, prior or concomitant medication use)
  • Participant has a history of unexplained syncope or a family history of sudden death due to long QT syndrome
  • Participant has renal impairment as indicated by an estimated glomerular filtration rate (GFR) <60 mL/min, calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
  • Participant tests positive for human immunodeficiency virus-1/2 antibody (HIV-1/2Ab) at Screening or within 3 months prior to the first dose of study medication

Specific exclusion criteria for study participants WITHOUT hepatic insufficiency

  • Participant has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) >1.0x upper limit of normal (ULN)
  • Participant has bilirubin >1.0xULN (isolated bilirubin >1.0xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
  • 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) Note: For participants with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, a baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic Case Report Form (eCRF). If participant has >ULN ALT, AST, or ALP that does not meet the exclusion limit at Screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the study participant must be discussed with the UCB Study Physician

Specific exclusion criteria for study participants WITH moderate hepatic insufficiency

  • Participant has acute liver failure of any etiology
  • Participant has biliary cirrhosis
  • Participant has used any drug indicated for the medical care of moderate hepatic insufficiency that is not established in dose and schedule for at least 14 days before the first liver function test (except paracetamol with a maximal dose of 2 g/day or with a maximum of 10 g over 15 days)

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): NCT04136444


Locations
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United States, Florida
Up0056 004
Orlando, Florida, United States, 32809
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: NCT04136444    
Other Study ID Numbers: UP0056
First Posted: October 23, 2019    Key Record Dates
Last Update Posted: April 21, 2020
Last Verified: April 2020
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: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by UCB Pharma ( UCB Biopharma S.P.R.L. ):
Padsevonil
Phase 1
Pharmacokinetic
PSL