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

Healthy Study Participants Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04136444
• Other study ID #: UP0056
• Status: Terminated
• Phase: Phase 1
• Start date: October 28, 2019
• Est. completion date: May 22, 2020

Study information

• Verified date: July 2021
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: May 22, 2020
• Est. primary completion date: May 22, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy Study Participants
• Impaired Hepatic Function

Intervention

Drug:
• Padsevonil
Padsevonil will be administered in predefined dosages.

Locations

Country	Name	City	State
United States	Up0056 004	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma S.P.R.L.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL)	Cmax is maximum observed plasma concentration.	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
Primary	Area Under the Plasma Concentration-time Curve From Time 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL)	AUC (0-t) is defined as area under the plasma concentration-time curve from time zero to time t.	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
Primary	Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity of a Single Dose Padsevonil (PSL)	AUC is defined as area under the plasma concentration-time curve from time 0 to infinity.	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
Primary	Maximum Observed Plasma Concentration at Steady-state (Cmax,ss) of Multiple Doses Padsevonil (PSL)	Cmax,ss is defined as maximum observed plasma concentration at steady-state.	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
Primary	Area Under the Concentration-time Curve (AUCtau) at Steady-state Over a Dosing Interval of Multiple Doses Padsevonil (PSL)	AUCtau is defined as area under the curve over a dosing interval at steady-state.	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	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	From Baseline until End of Study Visit (up to Day 18)
Secondary	Number of Participants With Serious Adverse Events (SAEs)	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.	From Baseline until End of Study Visit (up to Day 18)
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Discontinuation of the Study	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.	From Baseline until End of Study Visit (up to Day 18)