Clinical trial NCT04136444: A Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal or Moderately Impaired Hepatic Function
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Study Participants
Impaired Hepatic Function
Keywords: Padsevonil
Phase 1
Pharmacokinetic
PSL
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2019-10-23
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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)

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL)
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL)
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity of a Single Dose Padsevonil (PSL)
timeFrame: 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
measure: Maximum Observed Plasma Concentration at Steady-state (Cmax,ss) of Multiple Doses Padsevonil (PSL)
timeFrame: 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
measure: Area Under the Concentration-time Curve (AUCtau) at Steady-state Over a Dosing Interval of Multiple Doses Padsevonil (PSL)
timeFrame: 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
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From Baseline until End of Study Visit (up to Day 18)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Baseline until End of Study Visit (up to Day 18)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study
timeFrame: From Baseline until End of Study Visit (up to Day 18)
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Up0056 004
state: Florida
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: