- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04136444
A Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal or Moderately Impaired Hepatic Function
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)
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Florida
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Orlando, Florida, United States, 32809
- Up0056 004
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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:
- 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
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Healthy participants
Participants will receive assigned single and multiple doses of padsevonil.
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Padsevonil will be administered in predefined dosages.
Other Names:
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EXPERIMENTAL: Hepatically impaired participants
Participants will receive assigned single and multiple doses of padsevonil.
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Padsevonil will be administered in predefined dosages.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL)
Time Frame: Plasma samples were 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 is maximum observed plasma concentration.
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Plasma samples were 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
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Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL)
Time Frame: Plasma samples were 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
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AUC (0-t) is defined as area under the plasma concentration-time curve from time zero to time t.
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Plasma samples were 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
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Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity of a Single Dose Padsevonil (PSL)
Time Frame: Plasma samples were 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 is defined as area under the plasma concentration-time curve from time 0 to infinity.
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Plasma samples were 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
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Maximum Observed Plasma Concentration at Steady-state (Cmax,ss) of Multiple Doses Padsevonil (PSL)
Time Frame: On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose
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Cmax,ss is defined as maximum observed plasma concentration at steady-state.
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On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose
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Area Under the Concentration-time Curve (AUCtau) at Steady-state Over a Dosing Interval of Multiple Doses Padsevonil (PSL)
Time Frame: On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose
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AUCtau is defined as area under the curve over a dosing interval at steady-state.
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On Days 8, 9, 10 and 11 PK samples were taken predose. On Day 12, PK samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24 hours postdose
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame: From Baseline until End of Study Visit (up to Day 18)
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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.
A treatment-emergent adverse event was characterized according to the intake of the study medication.
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From Baseline until End of Study Visit (up to Day 18)
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Number of Participants With Serious Adverse Events (SAEs)
Time Frame: From Baseline until End of Study Visit (up to Day 18)
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A serious adverse event (SAE) is any untoward medical occurrence that at any dose:
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From Baseline until End of Study Visit (up to Day 18)
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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)
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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 was characterized according to the intake of the study medication.
TEAEs leading to discontinuation of the study are reported.
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From Baseline until End of Study Visit (up to Day 18)
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- UP0056
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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