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)
Overview
- Phase
- Phase 1
- Intervention
- Padsevonil
- Conditions
- Healthy Study Participants
- Sponsor
- UCB Biopharma S.P.R.L.
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL)
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
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.
Investigators
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:
- •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)
Arms & Interventions
Healthy participants
Participants will receive assigned single and multiple doses of padsevonil.
Intervention: Padsevonil
Hepatically impaired participants
Participants will receive assigned single and multiple doses of padsevonil.
Intervention: Padsevonil
Outcomes
Primary Outcomes
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.
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
AUC (0-t) is defined as area under the plasma concentration-time curve from time zero to time t.
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.
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
Cmax,ss is defined as maximum observed plasma concentration at steady-state.
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
AUCtau is defined as area under the curve over a dosing interval at steady-state.
Secondary Outcomes
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From Baseline until End of Study Visit (up to Day 18))
- Number of Participants With Serious Adverse Events (SAEs)(From Baseline until End of Study Visit (up to Day 18))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study(From Baseline until End of Study Visit (up to Day 18))