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

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Collaborators:

Information provided by (Responsible Party):

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Tracking Information

First Submitted Date ^ICMJE

September 14, 2018

First Posted Date ^ICMJE

October 3, 2018

Last Update Posted Date

October 3, 2018

Actual Study Start Date ^ICMJE

September 18, 2018

Estimated Primary Completion Date

March 22, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

The maximum observed plasma concentration (Cmax) for padsevonil (PSL)[ Time Frame: Blood samples will be 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 ]

Cmax: Maximum observed plasma concentration

The time to reach maximum concentration (tmax) for PSL[ Time Frame: Blood samples will be 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 ]

Time of observed Cmax (tmax)

The area under the curve (AUCt) over a dosing interval for PSL[ Time Frame: Blood samples will be 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 ]

AUCt: Area under the plasma concentration time curve over a dosing interval for PSL

The apparent total plasma clearance at steady-state (CL/Fss) for PSL[ Time Frame: Blood samples will be 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 ]

CL/Fss: Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes and F is the absolute oral bioavailability. Apparent oral clearance (CL/F) is obtained following oral administration at steady state

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Trough plasma concentration of Mono Hydroxy Derivate (MHD) in the inducers group before, during and after dosing to steady state with PSL[ Time Frame: Trough plasma samples will be taken prior to the morning dose of OXC on Day -1, Day 1 through Day 20 (+/-1) ]
Lowest concentration reached by the drug before the next dose is administered
The maximum observed plasma concentration (Cmax) for UCB1431322-000[ Time Frame: Blood samples will be 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 ]
Cmax: Maximum observed plasma concentration
The time to reach maximum concentration for UCB1431322-000[ Time Frame: Blood samples will be 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 ]
Time of observed Cmax (tmax)
The area under the curve (AUCt) over a dosing interval for UCB1431322-000[ Time Frame: Blood samples will be 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 ]
AUCt: Area under the plasma concentration time curve during a dosing interval
The ratio of PSL metabolite UCB1431322-000 to PSL based on the area under the curve (AUCt)[ Time Frame: Blood samples will be 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 ]
Ratio of UCB1431322-000 to PSL based on AUCt
The maximum observed plasma concentration (Cmax) for UCB1447499-000[ Time Frame: Blood samples will be 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 ]
Cmax: Maximum observed plasma concentration
The time to reach maximum concentration (tmax) for UCB1447499-000[ Time Frame: Blood samples will be 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 ]
Time of observed Cmax (tmax)
The area under the curve (AUCt) over a dosing interval for UCB1447499-000[ Time Frame: Blood samples will be 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 ]
AUCt: Area under the plasma concentration time curve during a dosing interval
The ratio of PSL metabolite UCB1447499-000 to PSL based on the area under the curve (AUCt)[ Time Frame: Blood samples will be 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 ]
Ratio of UCB1447499-000 to PSL based on AUCt
Incidence of adverse events (AE)[ Time Frame: From screening up to day 20 (+/-1) ]
An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage
Incidence of serious adverse events (SAE)[ Time Frame: From screening up to day 20 (+/-1) ]
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 as 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.

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

A Multicenter, Open-label, Parallel-group Study in Study Participants With Epilepsy, to Evaluate the Effect of Oxcarbazepine on the Pharmacokinetics, Safety, and Tolerability of Padsevonil

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.

Detailed Description

Study Type ^ICMJE

Interventional

Study Phase

Phase 1

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Basic Science

Condition ^ICMJE

Intervention ^ICMJE

Drug: Padsevonil
Padsevonil (PSL) will be dosed to steady state and the effect of background therapies on pharmacokinetics will be assessed
Drug: Oxcarbazepine
Concomitant administration of oxcarbazepine (OXC) at therapeutic dosage
Drug: Levetiracetam
Concomitant administration of levetiracetam (LEV) at therapeutic dosage
Drug: Lamotrigine
Concomitant administration of lamotrigine (LTG) at therapeutic dosage
Drug: Brivaracetam
Concomitant administration of brivaracetam (BRV) at therapeutic dosage

Study Arms

Experimental: Cohort 1
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.
Experimental: Cohort 2
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.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

March 22, 2019

Estimated Primary Completion Date

March 22, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria: - 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: 1. 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 2. 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) Exclusion Criteria: - 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)

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Netherlands

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

UCB Biopharma S.P.R.L.

Collaborators ^ICMJE

Investigators ^ICMJE

Study Director: UCB Cares 001 844 599 2273 (UCB)

PRS Account

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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