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

NCT04136444 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: UP0056
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Study Participants; Impaired Hepatic Function

Keywords

Padsevonil; Phase 1; Pharmacokinetic; PSL

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (3)

• 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)

Study Arms (2)

Healthy participants

EXPERIMENTAL

Participants will receive assigned single and multiple doses of padsevonil.

Drug: Padsevonil

Hepatically impaired participants

EXPERIMENTAL

Participants will receive assigned single and multiple doses of padsevonil.

Drug: Padsevonil

Interventions

Padsevonil DRUG

Padsevonil will be administered in predefined dosages.

Also known as: PSL, UCB0942

Healthy participants; Hepatically impaired participants

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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 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)

Sponsors & Collaborators

• UCB Biopharma S.P.R.L.: lead

Study Sites (1)

Up0056 004

Orlando, Florida, 32809, United States

Location

MeSH Terms

Interventions

padsevonil

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

+1844 599

Study Officials

• UCB Cares

  001 844 599 2273 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: October 23, 2019
• Study Start: October 28, 2019
• Primary Completion: May 22, 2020
• Study Completion: May 22, 2020
• Last Updated: July 28, 2021
• Results First Posted: July 28, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)