A Study in Participants With Epilepsy, to Evaluate the Pharmacokinetics, Safety and Tolerability of Oxcarbazepine on Padsevonil

NCT03695094 | Completed Phase 1 Results

• 2 other identifiers: UP00702018-001941-16
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of the study is to evaluate the effect of stable coadministered oxcarbazepine (OXC), on the pharmacokinetics (PK), safety, tolerability of padsevonil (PSL) and the plasma PK of PSL metabolites, UCB1431322-000 and UCB1447499-000, in study participants with epilepsy compared with study participants co-medicated with stable doses of levetiracetam (LEV), lamotrigine (LTG) or brivaracetam (BRV) therapy.

Conditions

Epilepsy

Keywords

Epilepsy; Phase 1; padsevonil

Outcome Measures

Primary Outcomes (4)

• The Maximum Observed Plasma Concentration (Cmax) of Padsevonil (PSL) During the Study

  The Cmax for Padsevonil in plasma was expressed in nanograms per milliliter (ng/mL).

  Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose

• The Time to Reach Maximum Concentration (Tmax) for Padsevonil During the Study

  The tmax for Padsevonil in plasma was expressed in hours (hr).

  Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose

• The Area Under the Plasma Concentration Time Curve (AUCtau) Over a Dosing Interval for PSL

  The AUCtau for Padsevonil in plasma was expressed in hours times nanograms per milliliter (hr\*ng/mL).

  Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose

• The Apparent Total Plasma Clearance at Steady-state (CL/Fss) for PSL During the Study

  The CL/Fss for Padsevonil in plasma was expressed in liters per hour (L/hr). Geometric Means and Coefficients of Variation (CVs) were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).

  Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose

Secondary Outcomes (11)

• Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL

  Trough plasma samples were taken prior to the morning dose of OXC on Day -1, Day 1 through Day 20 (+/-1)

• The Maximum Observed Plasma Concentration (Cmax) for UCB1431322-000 During the Study

  Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose

• The Time to Reach Maximum Concentration (Tmax) for UCB1431322-000 During the Study

  Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose

• The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1431322-000 During the Study

  Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose

• The Ratio of PSL Metabolite UCB1431322-000 to PSL Based on the Area Under the Curve (AUCtau) During the Study

  Blood samples were taken on Day 1 through Day 12, prior to the morning dose of PSL, at Day 13 prior to unit discharge and at Day 8 at pre-defined time points up to 12 hours post-dose

Study Arms (2)

Cohort 1

EXPERIMENTAL

Cohort 1 (Inducers): Study participants on stable therapy with oxcarbazepine (OXC) either as monotherapy or adjunctive to levetiracetam (LEV), lamotrigine (LTG), or brivaracetam (BRV). OXC may be used as monotherapy or in combination with 1 or more of LEV, LTG, or BRV. Padsevonil (PSL) will be dosed to steady state and the effect of background therapy on PSL pharmacokinetics will be assessed at steady state.

Drug: Padsevonil; Drug: Oxcarbazepine; Drug: Levetiracetam; Drug: Lamotrigine; Drug: Brivaracetam

Cohort 2

EXPERIMENTAL

Cohort 2 (Neutral): Study participants on stable therapy with lamotrigine (LTG), levetiracetam (LEV), or brivaracetam (BRV). LTG or LEV may be used as monotherapy or in combination with each other. BRV may only be used in combination with LTG. LTG or LEV may be used as monotherapy or in combination with each other. BRV may only be used in combination with LTG. Padsevonil (PSL) will be dosed to steady state (4.5 days) and the effect of background therapy on PSL pharmacokinetics will be assessed at steady state.

Drug: Padsevonil; Drug: Levetiracetam; Drug: Lamotrigine; Drug: Brivaracetam

Interventions

Padsevonil DRUG

Padsevonil (PSL) will be dosed to steady state and the effect of background therapies on pharmacokinetics will be assessed

Also known as: PSL, UCB0942

Cohort 1; Cohort 2

Oxcarbazepine DRUG

Concomitant administration of oxcarbazepine (OXC) at therapeutic dosage

Also known as: OXC

Cohort 1

Levetiracetam DRUG

Concomitant administration of levetiracetam (LEV) at therapeutic dosage

Also known as: LEV

Cohort 1; Cohort 2

Lamotrigine DRUG

Concomitant administration of lamotrigine (LTG) at therapeutic dosage

Also known as: LTG

Cohort 1; Cohort 2

Brivaracetam DRUG

Concomitant administration of brivaracetam (BRV) at therapeutic dosage

Also known as: BRV

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Study participant is male or female between 18 to 64 years of age, inclusive, with a diagnosis of epilepsy according to the International League Against Epilepsy (ILAE) classification
• Study participant is currently treated for epilepsy with stable doses of the following for at least 3 months:
• Inducers Group: Oxcarbazepine (OXC) (at least 1200 mg/day as monotherapy or in combination with brivaracetam (BRV) \[up to 200 mg/day\], levetiracetam (LEV) \[at least 1 g/day\] or lamotrigine (LTG) \[at least 150 mg/day\]); or
• Neutral (control) Group: LTG (at least 150 mg/day monotherapy or adjunctive to LEV or BRV), LEV (at least 1 g/day monotherapy or adjunctive to LTG), or BRV (up to 200 mg/day adjunctive to LTG)
• Study participant in the Inducers Group is taking OXC and has a trough OXC metabolite Mono Hydroxy Derivate (MHD) plasma level in the target range (≥12.0 to ≤35.0 mcg/mL)
• Study participant has clinical laboratory test results within the local reference ranges or values are considered as not clinically relevant by the Investigator and approved by the UCB Study Physician
• Study participant has a body mass index (BMI) of 18 to 35 kg/m², inclusive, with a body weight of at least 50 kg (male) or 45 kg (female)
• Female study participant has a negative serum pregnancy test at the Screening Visit and agrees to use an efficient form of contraception for the duration of the study (unless menopausal \[defined as no menses for 12 months without an alternative medical cause\]; a high follicle-stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy). -Male study participant agrees that, during the study period, when having sexual intercourse with a woman of childbearing potential, he will use an efficient barrier contraceptive (condom plus spermicide) AND that the respective partner will use an additional efficient contraceptive method (eg, oral pills, intrauterine device, intrauterine hormone-releasing systems, or diaphragm, and spermicide)

You may not qualify if:

• Study participant has participated in another study of an investigational medication (or a medical device) within the last 3 months before screening (or 5 half-lives, whichever is longer) or is currently participating in another study of an investigational medication (or a medical device)
• Study participant has a known hypersensitivity to any components of the IMP as stated in this protocol
• Study participant has any medical condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study
• Study participant has a history of status epilepticus during the last year
• Study participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline
• Study participant has received any prescription or nonprescription medicines, including enzyme inhibitors or inducers, over the counter (OTC) remedies, herbal and dietary supplements (including St. John's Wort), or vitamins up to 2 weeks or 5 half-lives of the respective drug (whichever is longer) before the first administration of IMP and during the clinical part of the study, unless required to treat an Adverse event (AE). This does not include allowed antiepileptic drugs (AEDs) per the protocol, oral contraceptives not exceeding 30 μg ethinyl estradiol or postmenopausal hormone replacement therapy or implants, patches, or IUDs/IUSs delivering progesterone (for female study participants)

Sponsors & Collaborators

• UCB Biopharma S.P.R.L.: lead

Study Sites (2)

Up0070 101

Sofia, Bulgaria

Location

Up0070 401

Leiden, Netherlands

Location

Related Publications (1)

• Chanteux H, MacPherson M, Kramer H, Otoul C, Okagaki T, Rospo C, De Bruyn S, Watling M, Bani M, Sciberras D. Overview of preclinical and clinical studies investigating pharmacokinetics and drug-drug interactions of padsevonil. Expert Opin Drug Metab Toxicol. 2024 Aug;20(8):841-855. doi: 10.1080/17425255.2024.2373108. Epub 2024 Jul 9.

  PMID: 38932723 DERIVED

MeSH Terms

Conditions

Epilepsy

Interventions

padsevonil; Oxcarbazepine; Levetiracetam; Lamotrigine; brivaracetam

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Carbamazepine; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Triazines

Results Point of Contact

• Title: UCB
• Organization: Cares

clinicaltrials@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: September 14, 2018
• First Posted: October 3, 2018
• Study Start: September 18, 2018
• Primary Completion: May 18, 2019
• Study Completion: May 30, 2019
• Last Updated: June 4, 2020
• Results First Posted: June 4, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1); NL (1)