Clinical trial NCT03695094: A Study in Participants With Epilepsy, to Evaluate the Pharmacokinetics, Safety and Tolerability of Oxcarbazepine on Padsevonil
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epilepsy
Keywords: Epilepsy
Phase 1
padsevonil
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2018-10-03
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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)

Primary outcomes:
measure: The Maximum Observed Plasma Concentration (Cmax) of Padsevonil (PSL) During the Study
timeFrame: 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
measure: The Time to Reach Maximum Concentration (Tmax) for Padsevonil During the Study
timeFrame: 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
measure: The Area Under the Plasma Concentration Time Curve (AUCtau) Over a Dosing Interval for PSL
timeFrame: 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
measure: The Apparent Total Plasma Clearance at Steady-state (CL/Fss) for PSL During the Study
timeFrame: 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:
measure: Trough Plasma Concentration of Mono Hydroxy Derivate (MHD) in the Inducers Group Before, During and After Dosing to Steady State With PSL
timeFrame: Trough plasma samples were taken prior to the morning dose of OXC on Day -1, Day 1 through Day 20 (+/-1)
measure: The Maximum Observed Plasma Concentration (Cmax) for UCB1431322-000 During the Study
timeFrame: 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
measure: The Time to Reach Maximum Concentration (Tmax) for UCB1431322-000 During the Study
timeFrame: 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
measure: The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1431322-000 During the Study
timeFrame: 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
measure: The Ratio of PSL Metabolite UCB1431322-000 to PSL Based on the Area Under the Curve (AUCtau) During the Study
timeFrame: 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
measure: The Maximum Observed Plasma Concentration (Cmax) for UCB1447499-000 During the Study
timeFrame: 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
measure: The Time to Reach Maximum Concentration (Tmax) for UCB1447499-000 During the Study
timeFrame: 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
measure: The Area Under the Curve (AUCtau) Over a Dosing Interval for UCB1447499-000 During the Study
timeFrame: 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
measure: The Ratio of PSL Metabolite UCB1447499-000 to PSL Based on the Area Under the Curve (AUCtau)
timeFrame: 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
measure: Percentage of Participants With at Least One Adverse Event (AE) During the Study
timeFrame: From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1)
measure: Percentage of Participants With at Least One Serious Adverse Event (SAE) During the Study
timeFrame: From screening (Day -28 to Day -2) up to end of study (EOS) visit day 20 (+/-1)
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Up0070 101
city: Leiden
country: Netherlands
facility: Up0070 401
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: